禽源H9N2 AIV对哺乳动物的感染及其引起肺部细胞因子与蛋白组变化的研究
|
摘要
H9N2禽流感（Avian Influenza，AI）在世界各地家禽群中流行，对养殖业造成了巨大经济损失。H9N2禽流感病毒（Avian Influenza Virus，AIV）是低致病性亚型，但是当其与其他病原混合感染时，病情加重，发病率、死亡率升高。不仅如此，自1999年以来中国大陆和香港地区相继报道了人感染H9N2的病例。虽然人感染H9N2流感病毒后只表现出轻微症状，但是由于该病毒的高度变异性以及容易与其他亚型流感病毒发生重组等特点，可能造成病毒的毒力增强。世界卫生组织（WHO）指出，H9N2被认为是潜在的可能造成人际间的流感爆发或大流行的禽流感病毒，对养殖产业和公共卫生具有极大的威胁。然而迄今为止，有关H9N2AIV在人群中流行情况的调查以及感染哺乳动物和人的应答以及组织病理反应的研究和报道较少，不利于该疫病的防治。
基于此，我们首先在山东地区高危人群中进行H9N2的血清学调查，结果表明禽类养殖人员中H9N2抗体阳性率为2.3%，这为该地区禽源H9N2感染人提供了血清学证据。本研究以H9N2山东禽源分离株为研究对象，深入研究其对哺乳动物的感染能力和病理变化；在此基础上以病变明显的肺脏为靶器官，通过荧光定量PCR、ELISA和Western方法对H9N2感染后的小鼠肺脏内细胞因子的表达变化进行研究；同时利用双向电泳（2DE）对小鼠肺脏组织中的差异蛋白质进行分析。从而为深入了解H9N2病毒引起的哺乳动物肺部损伤机制以及开发抗流感病毒药物靶标的研究提供理论基础。
本研究分以下四部分内容：
1. H9N2禽流感病毒血清学调查
为了解山东地区H9N2禽流感病毒在禽类从业人群中的感染状况，2011年12月至2012年2月，采集禽类从业人员382名及非从事动物工作的健康人员100人的全血样本，采用改进的血凝抑制和微量中和实验检测H9N2抗体。以≥40为临界值，通过HI或MN实验结果显示禽类从业人群有9例(9/382=2.3%)呈现H9N2抗体阳性，而100名非从事动物相关工作人员的H9N2抗体均为阴性。调查中，虽然未见H9N2感染的临床病例报告，但不排除潜伏感染或亚临床感染的可能性。调查表明禽类养殖业是感染禽流感的危险环境，对禽类从业人员健康状况的持续监测有助于评估H9N2禽流感病毒对人类健康和公共卫生的威胁。
2. H9N2AIV山东分离株基因序列特性分析及对哺乳动物的感染
参照GenBank上的H9N2AIV的全基因序列，设计分别扩增H9N2AIV8个基因片段的特异性引物，测定5株H9N2AIV山东分离株全基因序列并分析其遗传进化和分子特点，并以BABL/c小鼠和豚鼠为模型评价其致病性和传播能力。HA及NA进化树结果表明5株病毒均属于CK/Beijing谱系，其中2株病毒的HA具有人样受体结合特性（Leu234），3株病毒具有禽样受体结合特征（Gln234）。HA裂解位点分析表明，5株病毒均具有低致病性AIV特征；个别病毒的潜在糖基化位点存在增加或缺失现象。攻毒BABL/c小鼠后，CK/SD/W3和CK/SD/ch这2株病毒能够在小鼠肺部复制，平均病毒滴度可达到5.3±0.12log10TCID50/g和4.75±0.2log10TCID50/g；病理切片显示间质性肺炎病变，通过免疫组化在细支气管上皮细胞检测到病毒。在豚鼠模型的感染实验结果显示，CK/SD/W3和CK/SD/ch能在鼻甲、气管和肺脏复制，2株病毒在豚鼠鼻甲骨复制能力较在肺脏的复制能力高，平均病毒滴度分别为3.4±0.55log10TCID50/g和4.2±0.42Log10TCID50/g；且传播实验表明CK/SD/W3能通过直接接触传播，但并未证实其可通过气溶胶传播。本研究表明，山东分离株中病毒能不经适应就感染小鼠和豚鼠，具备感染哺乳动物的能力，应加强对流行毒株的监控以评估其对人类公共卫生的威胁。
3. H9N2AIV感染小鼠肺脏细胞因子的表达根据GenBank中小鼠的细胞因子和趋化因子的基因序列，选择其中的保守区，利用Premier5.0软件设计相应的引物，建立了相应的荧光定量PCR方法，该方法具有可靠的特异性、重复性和敏感性。利用该技术对感染H9N2(CK/SD/W3)的小鼠肺脏中11种细胞因子和趋化因子mRNA的表达进行检测，并结合ELISA和Western Blot验证相关细胞因子在蛋白水平的表达情况。研究结果显示，H9N2AIV感染的小鼠肺脏组织样本中IFN-γ，IL-6，MIP-1α，CCL5及IP-10mRNA含量有2倍~20倍不同程度升高，其中CCL-5在第2天增长15倍，IFN-γ在第6天增长20倍。应用ELISA和Westernblot对上升的全部或部分细胞因子进行了验证，其蛋白水平的表达趋势与荧光定量结果一致。H9N2AIV感染后的小鼠肺脏中，IFN-γ为主要抗病毒效应因子，而IP-10，IL-6，CCL-5和MIP-1α分别在促炎性反应中起一定作用。总之，本研究提供了H9N2AIV感染小鼠肺组织后免疫应答相关数据，为进一步了解H9N2对哺乳动物宿主的感染特性奠定了基础。
4. H9N2AIV感染小鼠肺脏的差异蛋白组学分析
利用蛋白组学研究方法双向凝胶电泳（2-DE），比较H9N2(CK/SD/W3)感染小鼠引起的肺脏蛋白质组差异。试验对病毒感染后12h和72h两个时间点进行检测，寻找攻毒组和对照组重叠比值（ratio值）大于2并且符合t检验（p<0.05）蛋白点，通过质谱分析共鉴定出31个蛋白，其中感染12h时有4个差异蛋白，72h有27个差异蛋白。这些蛋白与病毒-宿主相互作用有关，功能主要涉及骨架蛋白、应激反应、抗氧化反应、蛋白的转录或表达调节等。本研究结果表明上调的细胞骨架蛋白主要有微管相关蛋白CAP-Gly domain-containing linker protein1、Rab GTPase-activating protein1-like以及膜联蛋白annexin A4，它们通过复杂的囊泡运输和微管系统进行物质交换和信息传递。应激反应蛋白HSP27和三种抗氧化蛋白Chloride Intracellular Channel Protein1(CLIC1)，peroxiredoxin-6(Prx6)以及peroxiredoxin-2(Prx2)都显著上调，说明流感病毒的感染使内源性的氧化/抗氧化平衡受到干扰了，通过上调抗氧化蛋白来缓和氧化带来的损伤。Ubc protein，ubiquitin-B及ISG15蛋白与泛素-蛋白酶途径（UPP）相关。本实验为进一步认识流感病毒与宿主的相互作用，禽源流感病毒感染哺乳动物机制以及寻找新的流感药物靶标提供思路。
H9N2avian influenza virus (AIV) has been circulating worldwide in many avian speciesand resulted in great economic losses to poultry industries. Although its pathogenicity wastrivial, it could cause high morbidity and lethality to poultry when co-infected withother pathogens. More importantly, human cases of avian H9N2virus infection have beenreported in Hong Kong and mainland China since1999. H9N2influenza viruses of chickenorigin cause only mild symptoms in humans, but they have the pandemic and cross-speciespotential for the high level of genetic plasticity and ressortment with other subtypes. H9N2isalso regarded by the World Health Organization (WHO) as the next potential avian influenzasubtype that may have high prevalence in the future, and which may bring huge damagesupon global economies and public health. So far, data on seroprevalence of H9N2virusesamong humans and their infection in mammals are limited. This literature gap is veryunfavorable for the effective prevention and control of human H9N2infection.
Based on this, firstly, we investigated the seroprevalence of H9N2viruses amongpoultry workers with occupational exposure to domestic poultry in Shandong, China. Ninesubjects (2.3%) were positive for H9N2virus infection in the poultry workers in the currentstudy, which indicates that H9N2may have previously infected commercial laying poultryworker in Shandong, China. Therefore, in our study, avian-origin H9N2Shandong isolateswere used to investigate their infectivity and pathological changes in mammals. Then, thelungs were used as the target organ as their obvious lesions based on the above study. Theexpressions of cytokines in the lungs of H9N2-infected mice were examined by real-timepolymerase chain reaction(Real-time PCR), enzyme-linked immunosorbent assay (ELISA)and western blot. At the same time, proteomic analysis by using2DE on the lung tissues ofmice were also performed. This study will provide theoretical basis to the mechanisms of lung injury in mammals and the development of anti-influenza virus drug by providing drugtargets.
There are four parts of this study.
1Seroprevalence of avian influenza H9N2among poultry workers
This study was carried out to identify the seroprevalence of H9N2AIV among poultryworkers in Shandong, China. During December2011to February2012, a total of482subjectstook part in this study, including382poultry workers and100healthy residents withoutoccupational poultry exposure. Serum samples were collected and tested for the presence ofantibodies against H9N2AIV by hemagglutination inhibition (HI) and microneutralization(MN) assays. Nine subjects (9/382=2.3%) were positive for antibodies against H9N2AIVamong the poultry workers by either HI or MN assays using≥40cut-off, while none of the100healthy residents were seropositive. In conclusion, our study identified the H9N2avianinfluenza infections among poultry workers in Shandong, China, and continuous surveillanceof H9N2AIV infection in humans should be carried out to evaluate the threat to the publichealth.
2Gene analysis of H9N2AIV of Shandong isolates and their infectivity in mammals
The study was conducted to understand the evolution of H9N2subtype AIV isolatedfrom Shandong province and their pathogenicity to mammals. We analyzed the sequences of8segments of five H9N2AIVs isolated from Shandong province, and evaluated theirpathogenicity to mammals of the viruses by using BABL/c mice and guinea pigs model. TheHA and NA results indicated that all five strains belonged to CK/Beijing lineage. Two of thestrains possessed human-like receptor binding specificity (Leu234), while other threepossessed avain-like receptor binding specificity (Gln234). The HA cleavage site showed thatall strains were low pathogenic. Potential glycosylation sites varied among the viruses. Twoviruses could replicate in mice’s lung, caused interstitial pneumonia, and could be detected inbronchial epithelial cells by immunohistochemistry. The virus titers in mice lung were5.3±0.12log10TCID50/g and4.75±0.2log10TCID50/g.CK/SD/W3and CK/SD/ch could replicatein turbinate, trachea and lungs in the guinea pigs, the average virus titer of turbinate ranging3.4±0.55log10TCID50/g to4.2±0.42log10TCID50/g. The transmission experiments showedthat CK/SD/W3can spread by direct contact. Our study showed that H9N2Shandong isolatescan infect mice and guinea pigs without adaptation. It is essential to monitor the epidemicstrain in order to evaluate the public health threat to humans.
3Response profiles of cytokines and chemokines against avian H9N2influenza viruswithin the mouse lung
Specificity primers were designed according the gene sequences of cytokines andchemokines from the GenBank for real-time RT-PCR method. The results showed that thereal-time RT-PCR possessed high specificity and sensitivity. To obtain insight into the hostimmune responses to the avian H9N2virus, the expressions of11cytokines and chemokinesin the lungs of infected mice were examined by Real-time PCR, ELISA and Western. Afterinfection, there was a two-to20-fold mRNA induction of IFN-γ, IL-6, IP-10, CCL-5andMIP-1α; the concentrations of CCL-5and IFN-γ were, respectively, increased up to over15-fold at2dpi and20-fold at6dpi. Protein expressions of all or part of the five correspondingcytokines and chemokines (IFN-γ, IL-6, IP-10, CCL-5, and MIP-1α) were confirmed byELISA and western. We found that interferon gamma (IFN-γ) was the dominant antiviralcomponent, and interferon gamma-induced protein10kDa (IP-10), interleukin6(IL-6),chemokine (C-C motif) ligand5(CCL-5) and macrophage inflammatory protein-1alpha(MIP-1α) all played a role in pro-inflammatory responses to H9N2viruses. In conclusion, thisresearch can make us further understand the infection characteristics of H9N2virus inmammalian host by providing the data on mice lung immune responses to the avian H9N2virus.
4Proteomic analysis of the lungs of mice infected with H9N2AIV
To investigate the host response against H9N2infections, we performed proteomicanalysis by using2DE on the lung tissues of mice collected on12h and72h postinoculationwith SD/CK/W3or PBS as a control. Thirty-one differentially expressed (DE) proteins, ofwhich there are four different proteins at12h and27different proteins at72h.
These proteins are related to virus-host interactions and the functions includecytoskeletal proteins, stress response, antioxidant response, transcription or protein expressionregulation. The results indicated that cytoskeletal proteins are mainly regulated microtubule-associated protein CAP-Gly domain-containing linker protein1, Rab GTPase-activatingprotein1-like and annexin A4, which exchange material and transfer information through acomplex transport vesicles and microtubules. Stress response proteins HSP27and threeantioxidant protein Chloride Intracellular Channel Protein1(CLIC1), peroxiredoxin-6(Prx6)and peroxiredoxin-2(Prx2) were significantly increased, indicating that the influenza virusinfection may induce host cell oxidative stress. Ubc protein, ubiquitin-B and ISG15proteinare related to ubiquitin-proteasome pathway (UPP). Our data provide important informationregarding the interaction between influenza virus and host, which is useful to better understand the infection mechanisms of H9N2in mammals and development anti-influenzavirus drug targets.
基于此，我们首先在山东地区高危人群中进行H9N2的血清学调查，结果表明禽类养殖人员中H9N2抗体阳性率为2.3%，这为该地区禽源H9N2感染人提供了血清学证据。本研究以H9N2山东禽源分离株为研究对象，深入研究其对哺乳动物的感染能力和病理变化；在此基础上以病变明显的肺脏为靶器官，通过荧光定量PCR、ELISA和Western方法对H9N2感染后的小鼠肺脏内细胞因子的表达变化进行研究；同时利用双向电泳（2DE）对小鼠肺脏组织中的差异蛋白质进行分析。从而为深入了解H9N2病毒引起的哺乳动物肺部损伤机制以及开发抗流感病毒药物靶标的研究提供理论基础。
本研究分以下四部分内容：
1. H9N2禽流感病毒血清学调查
为了解山东地区H9N2禽流感病毒在禽类从业人群中的感染状况，2011年12月至2012年2月，采集禽类从业人员382名及非从事动物工作的健康人员100人的全血样本，采用改进的血凝抑制和微量中和实验检测H9N2抗体。以≥40为临界值，通过HI或MN实验结果显示禽类从业人群有9例(9/382=2.3%)呈现H9N2抗体阳性，而100名非从事动物相关工作人员的H9N2抗体均为阴性。调查中，虽然未见H9N2感染的临床病例报告，但不排除潜伏感染或亚临床感染的可能性。调查表明禽类养殖业是感染禽流感的危险环境，对禽类从业人员健康状况的持续监测有助于评估H9N2禽流感病毒对人类健康和公共卫生的威胁。
2. H9N2AIV山东分离株基因序列特性分析及对哺乳动物的感染
参照GenBank上的H9N2AIV的全基因序列，设计分别扩增H9N2AIV8个基因片段的特异性引物，测定5株H9N2AIV山东分离株全基因序列并分析其遗传进化和分子特点，并以BABL/c小鼠和豚鼠为模型评价其致病性和传播能力。HA及NA进化树结果表明5株病毒均属于CK/Beijing谱系，其中2株病毒的HA具有人样受体结合特性（Leu234），3株病毒具有禽样受体结合特征（Gln234）。HA裂解位点分析表明，5株病毒均具有低致病性AIV特征；个别病毒的潜在糖基化位点存在增加或缺失现象。攻毒BABL/c小鼠后，CK/SD/W3和CK/SD/ch这2株病毒能够在小鼠肺部复制，平均病毒滴度可达到5.3±0.12log10TCID50/g和4.75±0.2log10TCID50/g；病理切片显示间质性肺炎病变，通过免疫组化在细支气管上皮细胞检测到病毒。在豚鼠模型的感染实验结果显示，CK/SD/W3和CK/SD/ch能在鼻甲、气管和肺脏复制，2株病毒在豚鼠鼻甲骨复制能力较在肺脏的复制能力高，平均病毒滴度分别为3.4±0.55log10TCID50/g和4.2±0.42Log10TCID50/g；且传播实验表明CK/SD/W3能通过直接接触传播，但并未证实其可通过气溶胶传播。本研究表明，山东分离株中病毒能不经适应就感染小鼠和豚鼠，具备感染哺乳动物的能力，应加强对流行毒株的监控以评估其对人类公共卫生的威胁。
3. H9N2AIV感染小鼠肺脏细胞因子的表达根据GenBank中小鼠的细胞因子和趋化因子的基因序列，选择其中的保守区，利用Premier5.0软件设计相应的引物，建立了相应的荧光定量PCR方法，该方法具有可靠的特异性、重复性和敏感性。利用该技术对感染H9N2(CK/SD/W3)的小鼠肺脏中11种细胞因子和趋化因子mRNA的表达进行检测，并结合ELISA和Western Blot验证相关细胞因子在蛋白水平的表达情况。研究结果显示，H9N2AIV感染的小鼠肺脏组织样本中IFN-γ，IL-6，MIP-1α，CCL5及IP-10mRNA含量有2倍~20倍不同程度升高，其中CCL-5在第2天增长15倍，IFN-γ在第6天增长20倍。应用ELISA和Westernblot对上升的全部或部分细胞因子进行了验证，其蛋白水平的表达趋势与荧光定量结果一致。H9N2AIV感染后的小鼠肺脏中，IFN-γ为主要抗病毒效应因子，而IP-10，IL-6，CCL-5和MIP-1α分别在促炎性反应中起一定作用。总之，本研究提供了H9N2AIV感染小鼠肺组织后免疫应答相关数据，为进一步了解H9N2对哺乳动物宿主的感染特性奠定了基础。
4. H9N2AIV感染小鼠肺脏的差异蛋白组学分析
利用蛋白组学研究方法双向凝胶电泳（2-DE），比较H9N2(CK/SD/W3)感染小鼠引起的肺脏蛋白质组差异。试验对病毒感染后12h和72h两个时间点进行检测，寻找攻毒组和对照组重叠比值（ratio值）大于2并且符合t检验（p<0.05）蛋白点，通过质谱分析共鉴定出31个蛋白，其中感染12h时有4个差异蛋白，72h有27个差异蛋白。这些蛋白与病毒-宿主相互作用有关，功能主要涉及骨架蛋白、应激反应、抗氧化反应、蛋白的转录或表达调节等。本研究结果表明上调的细胞骨架蛋白主要有微管相关蛋白CAP-Gly domain-containing linker protein1、Rab GTPase-activating protein1-like以及膜联蛋白annexin A4，它们通过复杂的囊泡运输和微管系统进行物质交换和信息传递。应激反应蛋白HSP27和三种抗氧化蛋白Chloride Intracellular Channel Protein1(CLIC1)，peroxiredoxin-6(Prx6)以及peroxiredoxin-2(Prx2)都显著上调，说明流感病毒的感染使内源性的氧化/抗氧化平衡受到干扰了，通过上调抗氧化蛋白来缓和氧化带来的损伤。Ubc protein，ubiquitin-B及ISG15蛋白与泛素-蛋白酶途径（UPP）相关。本实验为进一步认识流感病毒与宿主的相互作用，禽源流感病毒感染哺乳动物机制以及寻找新的流感药物靶标提供思路。
H9N2avian influenza virus (AIV) has been circulating worldwide in many avian speciesand resulted in great economic losses to poultry industries. Although its pathogenicity wastrivial, it could cause high morbidity and lethality to poultry when co-infected withother pathogens. More importantly, human cases of avian H9N2virus infection have beenreported in Hong Kong and mainland China since1999. H9N2influenza viruses of chickenorigin cause only mild symptoms in humans, but they have the pandemic and cross-speciespotential for the high level of genetic plasticity and ressortment with other subtypes. H9N2isalso regarded by the World Health Organization (WHO) as the next potential avian influenzasubtype that may have high prevalence in the future, and which may bring huge damagesupon global economies and public health. So far, data on seroprevalence of H9N2virusesamong humans and their infection in mammals are limited. This literature gap is veryunfavorable for the effective prevention and control of human H9N2infection.
Based on this, firstly, we investigated the seroprevalence of H9N2viruses amongpoultry workers with occupational exposure to domestic poultry in Shandong, China. Ninesubjects (2.3%) were positive for H9N2virus infection in the poultry workers in the currentstudy, which indicates that H9N2may have previously infected commercial laying poultryworker in Shandong, China. Therefore, in our study, avian-origin H9N2Shandong isolateswere used to investigate their infectivity and pathological changes in mammals. Then, thelungs were used as the target organ as their obvious lesions based on the above study. Theexpressions of cytokines in the lungs of H9N2-infected mice were examined by real-timepolymerase chain reaction(Real-time PCR), enzyme-linked immunosorbent assay (ELISA)and western blot. At the same time, proteomic analysis by using2DE on the lung tissues ofmice were also performed. This study will provide theoretical basis to the mechanisms of lung injury in mammals and the development of anti-influenza virus drug by providing drugtargets.
There are four parts of this study.
1Seroprevalence of avian influenza H9N2among poultry workers
This study was carried out to identify the seroprevalence of H9N2AIV among poultryworkers in Shandong, China. During December2011to February2012, a total of482subjectstook part in this study, including382poultry workers and100healthy residents withoutoccupational poultry exposure. Serum samples were collected and tested for the presence ofantibodies against H9N2AIV by hemagglutination inhibition (HI) and microneutralization(MN) assays. Nine subjects (9/382=2.3%) were positive for antibodies against H9N2AIVamong the poultry workers by either HI or MN assays using≥40cut-off, while none of the100healthy residents were seropositive. In conclusion, our study identified the H9N2avianinfluenza infections among poultry workers in Shandong, China, and continuous surveillanceof H9N2AIV infection in humans should be carried out to evaluate the threat to the publichealth.
2Gene analysis of H9N2AIV of Shandong isolates and their infectivity in mammals
The study was conducted to understand the evolution of H9N2subtype AIV isolatedfrom Shandong province and their pathogenicity to mammals. We analyzed the sequences of8segments of five H9N2AIVs isolated from Shandong province, and evaluated theirpathogenicity to mammals of the viruses by using BABL/c mice and guinea pigs model. TheHA and NA results indicated that all five strains belonged to CK/Beijing lineage. Two of thestrains possessed human-like receptor binding specificity (Leu234), while other threepossessed avain-like receptor binding specificity (Gln234). The HA cleavage site showed thatall strains were low pathogenic. Potential glycosylation sites varied among the viruses. Twoviruses could replicate in mice’s lung, caused interstitial pneumonia, and could be detected inbronchial epithelial cells by immunohistochemistry. The virus titers in mice lung were5.3±0.12log10TCID50/g and4.75±0.2log10TCID50/g.CK/SD/W3and CK/SD/ch could replicatein turbinate, trachea and lungs in the guinea pigs, the average virus titer of turbinate ranging3.4±0.55log10TCID50/g to4.2±0.42log10TCID50/g. The transmission experiments showedthat CK/SD/W3can spread by direct contact. Our study showed that H9N2Shandong isolatescan infect mice and guinea pigs without adaptation. It is essential to monitor the epidemicstrain in order to evaluate the public health threat to humans.
3Response profiles of cytokines and chemokines against avian H9N2influenza viruswithin the mouse lung
Specificity primers were designed according the gene sequences of cytokines andchemokines from the GenBank for real-time RT-PCR method. The results showed that thereal-time RT-PCR possessed high specificity and sensitivity. To obtain insight into the hostimmune responses to the avian H9N2virus, the expressions of11cytokines and chemokinesin the lungs of infected mice were examined by Real-time PCR, ELISA and Western. Afterinfection, there was a two-to20-fold mRNA induction of IFN-γ, IL-6, IP-10, CCL-5andMIP-1α; the concentrations of CCL-5and IFN-γ were, respectively, increased up to over15-fold at2dpi and20-fold at6dpi. Protein expressions of all or part of the five correspondingcytokines and chemokines (IFN-γ, IL-6, IP-10, CCL-5, and MIP-1α) were confirmed byELISA and western. We found that interferon gamma (IFN-γ) was the dominant antiviralcomponent, and interferon gamma-induced protein10kDa (IP-10), interleukin6(IL-6),chemokine (C-C motif) ligand5(CCL-5) and macrophage inflammatory protein-1alpha(MIP-1α) all played a role in pro-inflammatory responses to H9N2viruses. In conclusion, thisresearch can make us further understand the infection characteristics of H9N2virus inmammalian host by providing the data on mice lung immune responses to the avian H9N2virus.
4Proteomic analysis of the lungs of mice infected with H9N2AIV
To investigate the host response against H9N2infections, we performed proteomicanalysis by using2DE on the lung tissues of mice collected on12h and72h postinoculationwith SD/CK/W3or PBS as a control. Thirty-one differentially expressed (DE) proteins, ofwhich there are four different proteins at12h and27different proteins at72h.
These proteins are related to virus-host interactions and the functions includecytoskeletal proteins, stress response, antioxidant response, transcription or protein expressionregulation. The results indicated that cytoskeletal proteins are mainly regulated microtubule-associated protein CAP-Gly domain-containing linker protein1, Rab GTPase-activatingprotein1-like and annexin A4, which exchange material and transfer information through acomplex transport vesicles and microtubules. Stress response proteins HSP27and threeantioxidant protein Chloride Intracellular Channel Protein1(CLIC1), peroxiredoxin-6(Prx6)and peroxiredoxin-2(Prx2) were significantly increased, indicating that the influenza virusinfection may induce host cell oxidative stress. Ubc protein, ubiquitin-B and ISG15proteinare related to ubiquitin-proteasome pathway (UPP). Our data provide important informationregarding the interaction between influenza virus and host, which is useful to better understand the infection mechanisms of H9N2in mammals and development anti-influenzavirus drug targets.
引文
陈锦辉，赵玉军，童贻刚.禽流感感染人的分子机制研究进展[J].畜牧兽医杂志.2007,26（1）：20-25.
陈慰峰.医学免疫学（第四版）[M].北京：人民卫生出版社，2006.
董书伟,荔霞,刘永明,王胜义,王旭荣,刘世祥,齐志明.蛋白质组学研究进展及其在中兽医学中的应用探讨[J].生物技术,2012,39(1):45-49
甘孟侯.禽流感[M].北京：北京农业出版社,2002,1-20.
郭霄峰,廖明,辛朝安. H9N2亚型禽流感病毒的致病特性研究.华南农业大学学报[J],2001,22(7):70-72
梁立滨,赵东明,李俊平,李雁冰,施建忠,姜永萍,陈化兰. H5N1亚型禽流感病毒感染小鼠肺组织蛋白质组分析[J].中国预防兽医学报,2011,33(4):261-264
刘洪雨,刘玉芬,于尔松.禽流感病毒的研究进展[J].畜牧兽医科技信息,2005,1:4.
刘增辉.病理染色技术[M].人民卫生出版社,北京,2000,157–158.
卢占军．感染马立克氏病病毒SPF鸡法氏囊蛋白质组学研究[D].扬州大学，扬州,2009．
吕进,王希良．流感病毒感染介导的免疫病理损伤研究进展[J]．生物化学与生物物理进展,2009,36:961-967．
宋琳莉,孟庆刚．流感病毒诱导宿主细胞凋亡的相关因子研究评述[J]．中华中医药学刊,2008,26:739-741．
韦平,秦爱建.重要动物病毒分子生物学[M].科学出版社,2008,4-5.
Adachi M., Matsukura S., Tokunaga H. and Kokubu F.. Expression of cytokines on humanbronchial epithelial cells induced by influenza virus A[J]. Int Arch Allergy Immunol,1997,113(1-3):307-311.
Akira S., Taga T. and Kishimoto T.. Interleukin-6in biology and medicine[M]. Adv Immunol,1993,54:1-78.
Alexander D. J.. A review of avian influenza in different bird species[J]. Vet Micro biol,2000a,74:3-13.
Alexander D. J. and Brown I. H.. Recent zoonoses caused by influenza A viruses[J]. Rev SciTech,2000b,19:197-125.
Alfonso P., Rivera J., Hernaez B., Alonso C. And Escribano J. M.. Identification of cellularproteins modified in response to African swine fever virus infection by proteomics[J].Proteomics,2004,4:2037-2046.
Andersson T., Johansson M., Bolmsjo G. and James P.. Automating MALDI sample plateloading. J Proteome Res,2007,6(2):894-896.
Aoki F. Y., Boivin G. and Roberts N.. Influenza virus susceptibility and resistance tooseltamivir[J]. Antivir Ther,2007,12:603-616.
Azad N. S., Rasool N., Annunziata C. M., Minasian L., Whiteley G. and Kohn E. C..Proteomics in clinical trials and practice: present uses and future promise[J]. Mol CellProteomics,2006,5:1819-1829.
Banks J., Special E. S., Moore E., Plowright L., Piccirillo A., Capua I., Cordioli P., Fioretti A.and Alexander D. J.. Changes in the haemagglutinin and the neuraminidase genes prior tothe emergence of highly pathogenic H7N1avian influenza viruses in Italy[J]. Arch Virol,2001,146(5):963-973.
Bi J., Deng G., Dong J., Kong F., Li X., Xu Q., Zhang M., Zhao L. and Qiao J.. Phylogeneticand molecular characterization of H9N2influenza isolates from chickens in Northern China from2007-2009[J]. PLoS One,2010,5: e13063.
Bouvier N. M., Lowen A. C. And Palese P.. Oseltamivir-resistant influenza A viruses aretransmitted efficiently among guinea pigs by direct contact but not by aerosol[J]. J Virol,2008,82:10052-10058.
Bright R. A., Medina M. J., Xu X. Y., Perez-Oronoz G., Wallis T. R., Davis X. M., PovinelliL., Cox N. J. and Klimov A. I.. Incidence of adamantance resistance among influenza A(H3N2) virus isolated worldwide from1994to2005: a cause for concern[J]. Lancet,2005,366(9495):1175-1181.
Brown E. G.. Influenza virus genetics. Biomed Phannacother.2000,54(4):196-209.
Brown I. H., Banks J., Manvell R. J., Essen S. C., Shell W., Slomka M., Londt B. andAlexander D.J.. Recent epidemiology and ecology of influenza A viruses in avian speciesin Europe and the Middle East[J]. Dev Biol(Basel),2006,124:45-50.
Butt K. M., Smith G. J., Chen H., Zhang L. J., Leung Y. H., Xu K. M., Lim W., Webster R. G.,Yuen K. Y., Peiris J. S. and Guan Y.. Human infection with an avian H9N2influenza Avirus in Hong Kong in2003[J]. J Clin Microbiol,2005,43:5760-5767.
Capua I., Mutinelli F., Marangon S. and Alexander D. J.. H7N1avian influenza in Italy (1999to2000) in intensively reared chickens and turkeys [J]. Avian Pathol,2000,29(6):537-543.
Cerretti D.P., Kozlosky C.J., Mosley B., Nelson N., Van Ness K., Greenstreet T. A., March C.J., Kronheim S. R., Druck T. and Cannizzaro L. A.. Molecular cloning of the interleukin-1beta converting enzyme[J]. Science,1992,256:97-100.
Chan M. C., Cheung C. Y., Chui W. H., Tsao S. W., Nicholls J. M., Chan Y. O., Chan R. W.,Long H. T., Poon L. L., Guan Y. and Peiris J. S.. Proinflammatory cytokine responsesinduced by influenza A (H5N1) viruses in primary human alveolar and bronchialepithelial cells[J]. Respir Res,2005,6:135
Chan R. W., Yuen K. M., Yu W. C., Ho C. C., Nicholls J. M., Peiris J. S. and Chan M. C..Influenza H5N1and H1N1virus replication and innate immune responses in bronchialepithelial cells are influenced by the state of differentiation[J]. PLoS ONE,2010,5:e8713
Chen W., Calvo P. A., Malide D., Gibbs J., Schubert., Bacik I., Basta S., O'Neill R., Schickli J.,Palese P., Henklein P., Bennink J. R. and Yewdell J. W.. A novel influenza A virusmitochondrial protein that induces cell death[J]. Nat Med,2001,7:1306-1312.
Chien C. Y., Tejero R., Huang Y., Zimmerman D. E., Ríos C. B., Krug R. M. and MontelioneG. T.. A novel RNA-binding motif in influenza A virus non-structural protein1. Nat Struct1997,4(11):891-895.
Choi Y. K., Ozaki H., Webby R. J., Webster R. G., Peiris J. S., Poon L., Butt C., Leung Y. H. C.and Guan Y.. Continuing evolution of H9N2influenza viruses in southeastern China [J]. JVirol,2004,78:8609-8614.
Coleman J. R.. The PB1-F2protein of Influenza A virus: increasing pathogenicity bydisrupting alveolar macrophages[J]. Virol J,2007,4:9.
Colman P. M., Laver W. G., Varqhese J. N., Baker A. T., Tulloch P. A., Air G. M. and WebsterR. G.. Three-dimensional structure of a complex of antibody with influenza virusneuraminidase[J]. Nature,1987,326(6111):358-363.
Concannon C. G., Gorman A. M. and Samali A.. On the role of Hsp27in regulatingapoptosis[J]. Apoptosis,2003,8:61-70.
Connor R. J., Kawaoka Y., Webster R. G. and Paulson J. C.. Receptor specificity in human,avian, and equine H2and H3influenza virus isolates[J]. Virology,1994,205(1):17-23.
Crouch E. and Wright J. R.. Surfactant proteins A and D and pulmonary host defense[J]. AnnuRev Physiol.2001;63:521-554.
Dairaghi D. J., Soo K. S., Oldham E. R., Premack B. A., Kitamura T., Bacon K. B. and SchallT. J.. RANTES-induced T cell activation correlates with CD3expression[J]. J Immunol,1998,160:426–433
Dawood F. S., Jain S., Finelli L., Shaw M. W., Lindstrom S., Garten R. J., Gubareva L. V., XuX., Bridges C. B. and Uyeki T. M.. Emergence of a novel swine-origin influenza A(H1N1) virus in humans[J]. N Engl J Med,2009,360(25):2605-2615.
de Jong M. D., Simmons C. P., Thanh T. T., Hien V. M., Smith G. J., Chau T. N., Hoang D. M.,Chau N. V., Khanh T. H., Dong V. C., Qui P. T., Cam B. V., Ha do Q., Guan Y., Peiris J. S.,Chinh N. T., Hien T. T. and Farrar J.. Fatal outcome of human influenza A (H5N1) isassociated with high viral load and hyper cytokinemia[J]. Nat Med,2006,12:1203-1207.
Dea S., Bilodeau R., Sauvagcau R., Montpetit C. and Martineau G. P.. Antigenic variant ofswine influenza virus causing proliferative and necrotizing pneumonia in pigs[J]. J VetDiag Invest,1992,4(4):380-392.
Del Prete G., De Carli M., Almerigogna F., Giudizi MG., Biagiotti R. and Romagnani S..Human IL-10is produced by both type1helper (Th1) and type2helper (Th2) T cellclones and inhibits their antigen-specific proliferation and cytokine production[J]. JImmunol,1993,150:353-360.
Dinarello C. A. and Wolff S. M.. The role of interleukin-1in disease[J]. N Engl J Med,1993,328:106-113.
Elster C., Larsen K., Gagnon J., Ruigrok R. W. and Baudin F.. Influenza virus M1proteinbinds to RNA through its nuelear localization signal[J]. J Gen Virol,1997,78(7):1589-1596.
Enelow R., Baramki D. F. and Borish L. C.. Inhibition of effector T lymphocytes mediatedthrough antagonism of IL-4[J]. J Allergy Clin Immunol,2004,113:560-562.
Enserink M. and Kaiser J.. Avian flu finds new mammal hosts[J]. Science,2004,(305):1385.
Fouchier R. A., Schneeberger P. M., Rozendaal F. W., Broekman J. M., Kemink S. A.,Munster V., Kuiken T., Rimmelzwaan G. F., Schutten M., Van Doornum G. J., Koch G.,Bosman A., Koopmans M. and Osterhaus A. D.. Avian influenza A virus (H7N7)associated with human conjunctivitis and a fatal case of acute respiratory distresssyndrome[J]. Proc Natl Acad Sci USA,2004,101(5):1356-1361.
Gabriel Q., Dauber B., Wolff T., Planz O., Klenk H. D. and Stech J.. The viral polymerasemediates adaptation of an avian influenza virus to a mammalian host[J]. Proc Natl AcadSci USA.2005,102(51):18590-18595.
Gambaryan A. S., Piskarev V. E., Yamskov I. A., Sakharov A. M., Tuzikov A. B., Bovin N. V.,Nifant'ev N. E. and Matrosovich M. N.. Human influenza virus recognition ofsialyloligosaccharides[J]. FEBS Lett,1995,366(1):57-60.
Gao G. and Luo H.. The ubiquitin–proteasome pathway in viral infections[J]. Can JPhysiol Pharmacol,2006,84:5-14.
Gao R., Cao B., Hu Y., Feng Z., Wang D. and Hu W.. Human infection with a novel avian-origin influenza A (H7N9) virus[J]. N Engl J Med,2013,368(20):1888-1897.
Gao Y., Zhang Y., Shinya K., Deng G., Jiang Y., Li Z., Gua Y., Tian G., Li Y., Shi J., Liu L.,Zeng X., Bu Z., Xia X., Kawaoka Y. and Chen H.. Identification of amino acids in HAand PB2critical for the transmission of H5N1avian influenza viruses in a mammalianhost[J]. PLoS Pathog,2009,5(12): e1000709.
Garcia-Sastre A.. Inhibition of interferonmediated antiviral responses by influenza A virusesand other negative-strand RNA viruses[J]. Virology,2001,279:375-384.
García-Sastre A., Egorov A., Matassov D., Brandt S., Levy D. E., Durbin J. E., Palese P. andMuster T.. Influenza A virus lacking the NS1gene replicates in interferon-deficientsystems[J]. Virology,1998,252:324-330.
Guo Y. J., Krauss S., Senne D. A., Mo I. P., Lo K. S., Xiong X. P., Norwood M., Shortridge K.F., Webster R. G., Guan Y.. Characterization of the pathogenicity of members of thenewly established H9N2influenza virus lineages in Asia[J]. Virology,2000,267:279-288.
Guo Y., Li J. and Cheng X.. Discovery of men infected by avian influenza A (H9N2) virus[J].Chinese J Exp Clin Virol,1999,13:105-108.
Hammer J. A. and Wu X. S.. Rabs grab motors: defining the connections between RabGTPases and motor proteins[J]. Current Opinion in Cell Biology,2002,14:69-75.
Haria C. and Dennis J. A.. Avian influenza and human health[J]. Acta Tropica,2002,83(1):1-6.
Harvey R. A., Zambon M. and Barday W. S.. Restrixtions to the adaption of influenza A virusH5hemagglutinin to the human host[J]. J Virol,2004,78(1):502-507.
Hatta M., Asano Y., Masunaqa K., Ito T., Okazaki K., Toyoda T., Kawaoka Y., Ishihama A.and Kida H.. Mapping of functional domains on influenza A virus RNA polymerase PB2molecule using monoclonal antibodies[J]. Arch Virol,2000,145(9):1947-1961.
Hatta M., Gao P., Halfmann P. and Kawaoka Y.. Molecular basis for high virulence of HongKong H5N1influenza A viruses[J]. Science,2001,293:1840-1842.
Helenius A.. Unpacking the incoming influenza virus[J]. Cell,1992,69:577-578.
Hillaire M. L., van Trierum S. E., Kreijtz J. H., Bodewes R., Geelhoed-Mieras M. M.,Nieuwkoop N. J., Fouchier R. A., Kuiken T., Osterhaus A. D. and Rimmelzwaan G. F..Cross-protective immunity against influenza pH1N12009viruses induced by seasonalinfluenza A (H3N2) virus is mediated by virus-specific T-cells[J]. J Gen Virol,2011,92:2339-2349.
Horimoto T. and Kawaoka Y.. Influenza: lessons from past pandemics, warnings from currentincidents[J]. Nat Rev Microbiol,2005,3(8):591-600.
Horimoto T., Rivera E., Pearson J., Senne D., Krauss S., Kawaoka Y. and Webster R. G.Origin and molecular changes associated with emergence of a highly pathogenic H5N2influenza virus in Mexico [J]. Virol,1995,213(1):223-230.
Hsiang T. Y., Zhao C. and Krug R. M.. Interferon-induced ISG15conjugation inhibitsinfluenza A virus gene expression and replication in human cells[J]. J Virol,2009,83:5971-5977.
Hulse D. J., Webster R. G., Russell R. J. and Pere D. R.. Molecular determinants within thesurface proteins involved in the pathogenicity of H5N1influenza viruses in chickens[J].J Virol,2004,78(18):9954-9964.
Ito T., Couceiro J. N., Kelm S., Baum L. G., Krauss S., Castrucci M. R., Donatelli I., Kida H.,Paulson J. C., Webster R. G. and Kawaoka Y.. Molecular basis for the generation in pigsof influenza A viruses with pandemic potential[J]. J Virol,1998,72(9):7367-7373.
Ito T. and Kawaoka Y.. Host-range barrier of influenza A viruses[J]. Vet Microbiol,2000,74(1-2):71-75.
Ito T., Suzuki Y., Mitnaul L., Vines A., Kida H. and Kawaoka Y.. Receptor specificity ofinfluenza A viruses correlates with the agglutination of erythrocytes from different animalspecies[J]. Virology,1997,227:493-499.
Jakel A., Reid K. B. and Clack H.. Surfactant protein A(SP-A) binds to phosphatidylserineand competes with annex in V binding on late apoptotic cells[J]. Protein Cell,2010,1(2):188-197．
Jia N., de Vlas S. J., Liu Y. X., Zhang J. S., Zhan L., Dang R. L., Ma Y. H., Wang X. J., Liu T.,Yang G. P., Wen Q. L., Richardus J. H., Lu S., Cao W. C.. Serological reports of humaninfections of H7and H9avian influenza viruses in northern China[J]. J Clin Virol,2009,44:225-229.
Jiao P., Tian G., Li Y., Deng G., Jiang Y., Liu C., Liu W., Bu Z., Kawaoka Y. and Chen H.. Asingle-amino-acid substitution in the NS1protein changes the pathogenicity of H5N1avian influenza viruses in mice[J]. J Virol,2008,82(3):1146-1154.
Jofre-Monseny L., Loboda A., Wagner A. E., Huebbe P., BoeschSaadatmandi C., JozkowiczA., Minihane A. M., Dulak J. and Rimbach G.. Effects of apoE genotype on macrophageinflammation and heme oxygenase-1expression[J]. Biochem Biophys Res Commun,2007,357:319-324.
Juknat A., Pietr M., Kozela E., Rimmerman N., Levy L., Coppola G., Geschwind D.and Vogel Z.. Differential transcriptional profiles mediated by exposure to thecannabinoids cannabidiol and D9-tetrahydrocannabinol in BV-2microglial cells[J]. Br JPharmacol,2012,165:2512-2528.
Julkunen I., Melén K., Nyqvist M., Pirhonen J., Sareneva T. and Matikainen S.. Inflammatoryresponses in influenza A virus infection[J]. Vaccine,2001,19: S32-S37．
Karpuzoglu E. and Ahmed S. A.. Estrogen regulation of nitric oxide and inducible nitric oxidesynthase (iNOS) in immune cells: implications for immunity, autoimmune diseases, andapoptosis[J]. Nitric Oxide,2006,15:177-186.
Kash J. C., Tumpey T. M., Proll S. C., Carter V., Perwitasari O., Thomas M. J., Basler C. F.,Palese P., Taubenberger J. K., García-Sastre A., Swayne D. E. and Katze M.G.. Genomicanalysis of increased host immune and cell death responses induced by1918influenzavirus[J]. Nature,2006,443:578-581.
Kawaguchi A., Naito T. and Nagato K.. Involvement of influenza virus PA subunit inassembly of functional RNA polymerase complexes[J]. J Virol,2005,79(2):732-744.
Kawaoka Y., Krauss S. and Webster R. G.. Avian-to-human transmission of the PB1gene ofinfluenza A viruses in the1957and1968pandemics[J]. J Virol,1989,63(11):4603-4608.
Kayali G., Setterquist S. F., Capuano A. W., Myers K. P., Gill J. S. and Gray G. C.. Testinghuman sera for antibodies against avian influenza viruses: horse RBC hemagglutinationinhibition vs. microneutralization assays[J]. J Clin Virol,2008,43:73-78.
Kimura Y.. Cytokines and chemokines induced by influenza virus infection[J]. Nippon Rinsho,2006,64(10):1822-1827．
King D. J.. Evaluation of different methods of inactivation of Newcastle disease virus andavian influenza virus in egg fluids and serum [J]. Avian Dis,1991,35(3):505-514.
Kishore U., Bernal A. L., Kamran M. F., Saxena S., Singh M., Sarma P. U., Madan T. andChakraborty T.. Surfactant proteins SP-A and SP-D in human health and disease[J]. ArchImmunol Ther Exp (Warsz).2005;53:399-417.
Klenk H. D. and Rott R.. The molecular biology of influenza virus pathogenieity[J]. AdvVirus Res,1988,34:247-281.
Kobasa D., Jones S. M., Shinya K., Kash J. C., Copps J., Ebihara H., Hatta Y., Kim J. H.,Halfmann P., Hatta M., Feldmann F., Alimonti J. B., Fernando L., Li Y., Katze M. G.,Feldmann H. and Kawaoka Y.. Aberrant innate immune response in lethal infection ofmacaques with the1918influenza virus[J]. Nature,2007,445:319-323.
Kobasa D., Takada A., Shinya K., Hatta M., Halfmann P., Theriault S., Suzuki H., NishimuraH., Mitamura K., Sugaya N., Usui T., Murata T., Maeda Y., Watanabe S., Suresh M.,Suzuki T., Suzuki Y., Feldmann H. and Kawaoka Y.. Enhanced virulence of influenza Aviruses with the haemagglutinin of the1918pandemic virus[J]. Nature,2004,431(7009):703-707.
Kogure T., Suzuki T., Takahashi T., Miyamoto D., Hidari K. I., Guo C. T., Ito T., Kawaoka Y.and Suzuki Y.. Human trachea primary epithelial cells express both sialyl(α2-3)Galreceptor for human parainfluenza virus type1and avian influenza viruses, and sialyl(α2-6)Gal receptor for human influenza viruses[J]. Glycoconj J,2006,23:101-106.
Koopmans M., Wilbrink B., Conyn M., Natrop G., van der Nat H., Vennema H, Meijer A, vanSteenbergen J., Fouchier R., Osterhaus A. and Bosman A.. Transmission of H7N7avianinfluenza A virus to human beings during a large outbreak in commercial poultry farms inthe Netherlands[J]. Lancet,2004,363:587-593.
Korteweg C. and Gu J.. Pathology, molecular biology, and pathogenesis of avian influenza A(H5N1) infection in humans[J]. Am J Pathol,2008,172(5):1155-1170.
Kostenko S. and Moens U.. Heat shock protein27phosphorylation: kinases, phosphatases,functions and pathology[J]. Cell Mol Life Sci,2009,66(20):3289-3307.
Krug R. M., Yuan W., Noah D. L. and Latham A. G.. Intracellular warfare between humaninfluenza viruses and human cells: the roles of the viral NS1protein[J]. Virology,2003,309:181-189.
Kuchipudi S. V., Nelli R., White G. A., Bain M., Chang K. C. and Dunham S.. Differences ininfluenza virus receptors in chickens and ducks: Implications for interspeciestransmission[J]. J Mol Genet Med,2009,3(1):143-51.
Labadie K., Dos Santos Afonso E., Rameix-Welti M. A., van der Werf S. and Naffakh N..Host-range determinants on PB2protein of influenza A viruses control the interactionbetween the viral polymerase and nucleoprotein in human cells[J]. Virology,2007,362(2):271-282.
Lee S. J., Kim K. H., Park J. S., Jung J. W., Kim Y. H., Kim S. K., Kim W. S., Goh H. G., KimS. H., Yoo J. S., Kim D. W. and Kim K. P.. Comparative analysis of cell surface proteinsin chronic and acute leukemia cell lines[J]．Biochem Biophys Res Commun,2007:357:620-626．
Lee Y. J., Shin J. Y., Song M. S., Lee Y. M., Choi J. G., Lee E. K., Jeong O. M., Sung H. W.,Kim J. H., Kwon Y. K., Kwon J. H., Kim C. J., Webby R. J., Webster R. G. and Choi Y. K..Continuing evolution of H9influenza viruses in Korean poultry[J].Virology,2007,359:313-323.
Li S., Schulman J., Itamura S. and Palese P.. Glycosylation of neuraminidase determines theneurovirulence of influenza A/WSN/33virus. J Virol,1993,67:6667-6673.
Li X., Qi W., He J., Ning Z., Hu Y., Tian J., Jiao P., Xu C., Chen J., Richt J., Ma W. and LiaoM.. Molecular basis of efficient replication and pathogenicity of H9N2avian influenzaviruses in mice[J]. PLoS One,2012,7(6): e40118.
Li Z., Chen H., Jiao P., Deng G., Tian G., Li Y., Hoffmann E., Webster R. G., Matsuoka Y. andYu K.. Molecular basis of replication of duck H5N1influenza viruses in a mammalianmouse model[J]. J Virol,2005;79:12058-12064.
Liu H., Liu X., Cheng J., Peng D., Jia L. and Huang Y.. Phylogenetic analysis of thehemagglutinin genes of twenty-six avian influenza viruses of subtype H9N2isolated fromchickens in China during1996–2001[J]. Avian Dis,2003,47:116-127.
Liu N., Song W., Wang P., Lee K., Chan W., Chen H, and Cai Z.. Proteomics analysis ofdifferential expression of cellular proteins in response to avian H9N2virus infection inhuman cells[J]. Proteomics,2008,8(9):1851-1858.
Livak K. J. and Schmittgen T. D.. Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the2ΔΔCT Method[J]. Methods,2001,25(4):402-408.
Lowen A. C., Mubareka S., Steel J. and Palese P.. Influenza virus transmission is dependenton relative humidity and temperature[J]. PLoS Path,2007,3(10):1470-1476.
Lowen A. C., Mubareka S., Tumpey T. M., Garcia-Sastre A. and Palese P.. The guinea pig as atransmission model for human influenza viruses[J]. Proc Natl Acad Sci U S A,2006,103:9988-9992.
MacNeill C., Umstead T. M., Phelps D. S., Lin Z.W. and Floros J.. Surfactant protein A, aninnate immune factor, is expressed in the vaginal mucosa and is present in vaginal lavagefluid[J]. Immunology,2004,111:91-99.
Maghazachi A. A., Vujanovic N. L., Herberman R. B. and Hiserodt J. C.. Lymphokine-activated killer cells in rats. IV. Developmental relationships among large agranularlymphocytes, large granular lymphocytes, and lymphokine-activated killer cells[J]. JImmunol,1988,140(8):2846-2852.
Mahalingam S., Friedland J. S., Heise M. T., Rulli N. E., Meanger J., Lidbury B. A..Chemokines and viruses: friends or foes?[J]. Trends Microbiol,2003,11(8):383-391.
Maines T. R., Lu X. H., Erb S. M., Edwards L., Guarner J., Greer P. W., Nguyen D. C.,Szretter K. J., Chen L. M., Thawatsupha P., Chittaganpitch M., Waicharoen S., Nguyen D.T., Nguyen T., Nguyen H. H., Kim J. H., Hoang L. T., Kang C., Phuong L. S., Lim W.,Zaki S., Donis R. O., Cox N. J., Katz J. M. and Tumpey T. M.. Avian influenza (H5N1)viruses isolated from humans in Asia in2004exhibit increased virulence in mammals[J].J Virol,2005,79:11788-11800.
Masuda H., Suzuki H., Oshitani H., Saito R., Kawasaki S., Nishikawa M. and Satoh H..Incidence of amantadine-resistant influenza A viruses in sentinel surveillance sites andnursing homes in Niigata, Japan[J]. Micrebiol Immunol,2000,44(10):833-839.
Matrosovich M. N., Krauss S. and Webster R. G.. H9N2influenza A viruses from poultry inAsia have human virus-like receptor specificity[J]. Virology,2001,281(2):156-162.
Matrosovich M. N., Matrosovich T. Y., Gray T., Roberts N. A. and Hans-Dieter Klenk..Human and avian influenza viruses target different cell types in cultures of human airwayepithelium[J]. Proc Natl Acad Sci USA,2004,101(13):4620-4624.
Matrosovich M. N., Matrosovich T. Y., Gray T., Roberts N. A. and Klenk H. D..Neuraminidase is important for the initiation of influenza virus infection in human airwayepithelium [J]. J Virol,2004,78(22):12665-12667.
Matsukura S., Kokubu F., Noda H., Tokunaga H. and Adachi M.. Expression of IL-6, IL-8,and RANTES on human bronchial epithelial cells, NCI-H292, induced by influenza virusA[J]. J Allergy Clin Immunol,1996,98:1080-1087.
Matsushima-Nishiwaki R., Takai S., Adachi S., Minamitani C., Yasuda E., Noda T., Kato K.,Toyoda H., Kaneoka Y., Yamaguchi A., Kumada T. and Kozawa O.. Phosphorylated heatshock protein27represses growth of hepatocellular carcinoma via inhibition ofextracellular signal-regulated kinase[J]. J Biol Chem,2008,283(27):18852-18860.
Mittal N. and Sanyal S. N.. Exogenous surfactant suppresses inflammation in experimentalendotoxin-induced lung injury[J]. J Environ Pathol Toxicol Oncol,2009,28(4):341-349．
Mumford E., Bishop J., Hendrickx S. and Embarek P. B.. Perdue M Avian influenzaH5N1:risks at the human-animal interface[J]. Food Nutr Bull,2007,28: S357-363.
Muramoto Y., Le T. Q., Phuong L. S., Nguyen T., Nguyen T. H., Sakai-Tagawa Y., HorimotoT., Kida H. and Kawaoka Y.. Pathogenicity of H5N1Influenza A viruses isolated inVietnam between late2003and2005[J]. J Vet Med Sci,2006,68(7):735-737.
Nang N. T., Lee J. S., Song B. M., Kang Y. M., Kim H. S. and Seo S.H.. Induction ofinflammatory cytokines and toll-like receptors in chickens infected with avian H9N2influenza virus[J]. Vet Res,2011,42:64.
Narasimhan J., Potter J. L. and Haas A. L.. Conjugation of the15-kDa interferon-inducedubiquitin homolog is distinct from that of ubiquitin[J]. J Biol Chem,1996,271:324-330.
Nelli R. K., Kuchipudi S. V., White G. A., Perez B. B., Dunham S. P. and Chang K. C..Comparative distribution of human and avian type sialic acid influenza receptors in thepig[J]. BMC Vet Res,2010,6:4.
Nili H. and Asasi K.. Natural cases and an experimental study of H9N2avian influenza incommercial broiler chickens of Iran[J]. Avian Pathol,2002,31(3):247-252.
Ohuchi M., Orlich M., Ohuchi R., Simpson B. E., Garten W., Klenk H. D. and Rott R..Mutations at the cleavage site of the hemagglutinin after the pathogenicity of influenzavirus A/chick/Penn/83(H5N2)[J]. Virology,1989,168(2):274-280.
Osiak A., Utermohlen O., Niendorf S., Horak I. and Knobeloch KP.. ISG15, an interferon-stimulated ubiquitin-like protein, is not essential for STAT1signaling and responsesagainst vesicular stomatitis and lymphocytic choriomeningiti virus[J]. Mol Cell Biol,2005,25:6338-6345.
Ostler T., Davidson W. and Ehl S.. Virus clearance and immunopathology by CD8+T cellsduring infection with respiratory syncytial virus are mediated by IFN-γ[J]． Eur JImmunol,2002,32:2117-2123．
Palese P. and Young J. F.. Variation of influenza A, B, and C viruses[J]. Science1982,(215):1468-1474.
Pandey A. and Mann M.. Proteomics to study genes and genomes[J]. Nature,2000,405(6788):837-846．
Paul W. E. and Ohara J.. B-cell stimulatory factor-1/interleukin4[J]. Annu Rev Immunol,1987,5:429-459
Peiris J. S., de Jong M. D. and Guan Y.. Avian influenza virus(H5N1):a threat to humanhealth[J]. Clin Mierobiol Rev,2007,20:243-267.
Peiris J. S., Yu W. C., Leung C. W., Cheung C. Y., Ng W. F., Nicholls J. M., Ng T. K., Chan K.H., Lai S. T., Lim W. L., Yuen K.Y. and Guan Y.. Re-emergence of fatal human influenzaA subtype H5N1disease[J]. Lancet,2004;363:617-619.
Peiris J. S., Guan Y., Markwell D., Ghose1P., Webster R. G. and Shortridge1K. F..Cocirculation of avian H9N2and contemporary Human H3N2influenza A virus in pigsin Southeastern China: potential for genetic reassortment[J]. J Virol,2001,75(20):9679-9686.
Peiris M., Yuen K. Y., Leung C. W., Chan K. H., Ip P. L., Lai R. W. and Orr W. K.. ShortridgeKF Human infection with influenza H9N2[J]. Lancet,1999,354:916-917.
Pelkmans L., Puntener D. and Helenius A.. Local actin polymerization and dynaminrecruitment in SV40-induced internalization of caveolae[J]. Science,2002,296:535-539.
Perdue M. L. and Suarez D. L.. Structural features of the avian influenza virus hemagglutininthat influence virulence [J]. Vet Microbiol.2000,74(1-2):77-86.
Perdue M. L. and Swayne D. E.. Public health risk from avian influenza virus[J]. Avian Dis,2005,49:317-327.
Perrone L. A., Plowden, J. K., Garcia-Sastre A., Katz, J. M. and Tumpey T. M. H5N1and1918pandemic influenza virus infection results in early and excessive infiltration ofmacrophages and neutrophils in the lungs of mice[J]. PLoS Pathog.2008,4:e1000115
Pertmer T. M., Oran A. E., Moser J. M., Madorin C. A. and Robinson H. L.. DNA vaccinesfor influenza virus: differential effects of maternal antibody on immune responses tohemagglutinin and nucleoprotein[J]. J Virol,2000,74(17):7787-7793.
Pillai S. P. and Lee C. W.. Species and age related differences in the type and distribution ofinfluenza virus receptors in different tissues of chickens, ducks and turkeys[J]. Virol J2010,7:5.
Poon L. M., Pritlove D. C., Fodor E. and Brownlee G. G.. Direct evidence that the Poly(A) tailof influenza A virus is synthesized by reiterative copying of a U track in the virion RNAtemplate[J]. J Virol,1999,73(4):3473-3476.
Qu B., Li X., Gao W., Sun W., Jin Y., Cardona C. J. and Xing Z.. Human intestinal epithelialcells are susceptible to influenza virus subtype H9N2[J]. Virus Res,2012,163:151-159.
Reed L. J. and Muench H.. A simple method of estimating fifty percent endpoints[J]. Am JHyg,1938,27:493-497.
Reid A. H., Fanning T. G., Hultin J. V. and Taubenberger J. K.. Origin and evolution of the1918"Spanish" influenza virus hemagglutinin gene[J]. Proc Natl Acad Sci USA,1999,96(4):1651-1656.
Richard M., Ferraris O., Erny A., Barthélémy M., Traversier A., Sabatier M., Hay A., Lin Y. P.,Russell R. J. and Lina B.. Combinatorial effect of two framework mutations (E119V andI222L) in the neuraminidase active site of H3N2influenza virus on esistance tooseltamivir[J]. Antimicrob Agents Chemother,2011,55(6):2942-2952.
Rogers G. N., Paulson J. C., Daniels R. S., Skehel J. J., Wilson I. A. and Wiley D. C.. Singleamino acid substitutions in influenza haemagglutinin change receptor specificity[J].Nature,1983,304:76-78.
Rogers G. N. and Paulson J. C.. Receptor determinants of human and animal influenza virusisolates: differences in receptor specificity of the H3hemagglutinin based on species oforigin[J]. Virology,1983,127:361-373.
Samji T.. Influenza A: understanding the viral life cycle[J]. Yale J Biol Med,2009,82(4):153-159.
Santis R. D., Faggioni G., Ciammaruconi A., et al. A FRET based melting curve analysis todetect nucleotide variations in HA receptor-binding site of H5N1virus[J]. Mol CellProbes,2010,24(5):298-302.
Seabra M. C., Coudrier E.. Rab GTPases and myosin motors in organelle motility[J]. Traffic,2004,5:393-399.
Shinya K., Ebinal M.,Yamada S., et a1. Influenza virus receptor in the humanairway[J]．Narute,2006,440:435-437.
Shohei K., Ken J. I., Cevayir C., et al. Innate immune response to viral infection[J]. Cytokine,2008,43(3):336-341.
Simonsen L., Clarke M. J., Schonberger L. B., Arden N. H., Cox N. J.,&Fukuda K..Pandemic versus epidemic influenza mortality: a pattern of changing age distribution[J]. JInfect Dis,1998,178(1):53-60.
Skehel J. J., Wiley D. C.. Receptor binding and membrane fusion in virus entry: the influenzahemagglutinin[J]. Annu Rev Biochem,2000,(69):531-569.
Skehel J. J.. Polypeptied synthesis in influenza virus-infected cells[J]. Virology,1972,49:23-36.
Sorrell E. M., Wan H., Araya Y., Song H. and Perez D. R.. Author Affiliations. Minimalmolecular constraints for respiratory droplet transmission of an avian-human H9N2influenza A virus[J]. Proc Natl Acad Sci USA,2009,106(18):7565-7570.
Spittler A., Razenberger M.,Kupper H., Kaul M., Hackl W., Boltz-Nitulescu G., Függer R. andRoth E.. Relationship between interleukin-6plasma concentration in patients with sepsis,monocyte phenotype, monocyte phagocytic properties and cytokine production[J]. ClinInfect Dis,2000,31:1338-1342.
Stegeman A., Bouma A. and Elbers A. R.. Avian influenza A virus (H7N7) epidemic in TheNetherlands in2003: course of the epidemic and effectiveness of control measures[J]. JInfect Dis,2004,190(12):2088-2095.
Steinhauer D. A.. Role of Hemagglutinin Cleavage for the Pathogenieity of InfluenzaVirus[J].Virology,1999,258: l-20.
Stevens J., Blixt O., Tumpey T. M., Taubenberger J. K., Paulson J. C. and Wilson I. A..Structure and receptor specificity of the hemagglutinin from an H5N1influenza virus[J].Science,2006,312:404-410.
Stolp B. and Fackler O. T.. How HIV Takes Advantage of the Cytoskeleton in Entry andReplication[J]. Viruses-Basel,2011,3:293-311.
Subbarao E. K., London W. and Murphy B. R.. A single amino acid in the PB2gene ofinfluenza A virus is a determinant of host range[J]. J Virol,1993,67(4):1761-1764.
Sun K. and Metzger D. W.. Inhibition of pulmonary antibacterial defense by interferon-γduring recovery from influenza infection[J]．Nat Med,2008,14:558-564.
Suzuki Y., Ito T., Suzuki T., Holland R. E., Chambers T. M., Kiso M., Ishida H. and KawaokaY.. Sialic acid species as a determinant of the host range of influenza A viruses[J]. J Virol,2000,74:11825-11831.
Tarendeau F., Boudet J., Guilligay D., Mas P. J., Bougault C. M., Boulo S., Baudin F.,Ruigrok R. W., Daigle N., Ellenberg J., Cusack S., Simorre J. P. and Hart D. J.. Structureand nuclear import function of the C-terminal domain of influenza virus polymerase PB2subunit[J]. Nature,2007,14(3):229-233.
Tong A., Wu L., Lin Q., Lau Q. C., Zhao X., Li J., Chen P., Chen L., Tang H., Huang C. andWei Y. Q.. Proteomic analysis of cellular protein alterations using a hepatitis B virus-producing cellular model[J]. Proteomics,2008,8:2012-2023
Twu K. Y., Kuo R. L., Marklund J. and Krug R. M.. The H5N1influenza virus NS genesselected after1998enhance virus replication in mammalian cells[J]. J Virol,2007,81(15):8112-8121.
Bremner K. H., Scherer J., Yi J. L., Vershinin M., Gross S. P. and Vallee R. B.. Adenovirustransport via direct interaction of cytoplasmic dynein with the viral capsid hexonsubunit[J]. Cell Host Microbe,2009,6:523-535.
Van Reeth K.. Cytokines in the pathogenesis of influenza. Vet Microbiol.2000;74:109-116.
Van Snick J.. Interleukin-6: an overview[J]. Annu Rev Immunol,1990,8:253-278.
Vester D., Rapp E., Gade D., Genzel Y. and Reichl U.. Quantitative analysis of cellularproteome alterations in human influenza A virus-infected mammalian cell lines[J].Proteomics,2009,9(12):3316-3327.
Vey M., Orlich M., Adler S., Klenk H. D., Rott R. and Garten W.. Hemagglutinin activationof pathogenic avian viruses of serotype H7requires the protease recognition motif R-X-K/R-R [J]. Virology,188(1):408-413.
Viswanathan K., Koh X., Chandrasekaran A., Pappas C., Raman R., Srinivasan A., Shriver Z.,Tumpey T. M. and Sasisekharan R.. Determinants of glycan receptor specificity of H2N2influenza A virus hemagglutinin[J]. PLoS ONE,2010,5(10): e13768.
Wan H. and Perez D. R.. Quail carry sialic acid receptors compatible with binding of avianand human influenza viruses[J]. Virology,2006,346(2):278-286.
Wang M., Fu C. X. and Zheng B. J.. Antibodies against H5and H9avian influenza amongpoultry workers in China[J]. N Engl J Med,2009,360:2583-2584
Wasinger V. C., Cordwell S. J., Cerpa-Poljak A., Yan J. X., Gooley A. A., Wilkins M. R.,Duncan M. W., Harris R., Williams K. L. and Humphery-Smith I.. Progress with gene-product mapping of the Mollicutes: Mycoplasma genitalium[J]. Electrophoresis,1995,16:1090-1094.
Watanabe K., Fuse T., Asano I., Tsukahara F., Maru Y., Nagata K., Kitazato K. and KobayashiN.. Identification of Hsc70as an influenza virus matrix protein (M1) binding factorinvolved in the virus life cycle[J]. FEBS Lett,2006,580:5785-5790.
Webster R. G., Air G. M., Metzger D. W., Colman P. M., Varghese J. N., Baker A. T. and LaverW. G. Antigenic structure and variation in an influenza virus N9neuraminidase [J]. JVirol,1987,61(9):2910-2916.
Webster R. G. and Laver W. G. The origin of pandemic influenza [J]. Bull World Health Organ,1972,47(4):449-452.
Webster R. G., Bean W. J., Gorman O. T., Chambers T. M. and Kawaoka Y.. Evolution andecology of influenza A viruses[J]. Microbiol Rev,1992,56(1):152-179.
Webster R. G. and Laver W. G.. The origin of pandemic influenza[J]. Bull World Health Organ,1972,47(4):449-452.
Webster R. G., Yakhno M., Hinshaw V. S., Bean W. J. and Murti K. G. Intestinal influenza:replication and characterization of influenza viruses in ducks [J]. Virology,1978,84(2):268-278.
WHO. Cumulative Number of Confirmed Human Cases of Avian Influenza A/(H5N1)Reported to WHO. Geneva: WHO,2008.
Wong S. S. and Yuen K. Y.. Avian influenza virus infections in humans[J]. Chest,2006,129:156-168.
Wu R., Kausar H., Johnson P., Montoya-Durango D. E., Merchant M. and Rane M. J.. Hsp27regulates Akt activation and polymorphonuclear leukocyte apoptosis by scaffolding MK2to Akt signal complex[J]. J Biol Chem,2007,282(30):21598-21608.
Xing Z., Harper R., Anunciacion J., Yang Z., Gao W., Qu B., Guan Y. and Cardona C. J.. Hostimmune and apoptotic responses to avian influenza virus H9N2in humantracheobronchial epithelial cells[J]. Am J Respir Cell Mol Biol,2011,44:24-33.
Xu R. and Wilson I.. Structural characterization of an early fusion intermediate of influenzavirus hemagglutinin[J]. J Virology,2011,85(10):5172-5182.
Yamada S. Y., Suzuki Y. S., Suzuki T. S, Yamada S., Suzuki Y., Suzuki T., Le M. Q., Nidom C.A., Sakai-Tagawa Y., Muramoto Y., Ito M., Kiso M., Horimoto T., Shinya K., Sawada T.,Kiso M., Usui T., Murata T., Lin Y., Hay A., Haire L. F., Stevens D. J., Russell R. J.,Gamblin S. J., Skehel J. J. and Kawaoka Y.. Hemagglutinin mutations responsible for thebinding of H5N1influenza A viruses to human-type receptors[J]. Nature,2006,444(16):378-382.
Yang H., Chen L. M., Carney P. J., Donis R. O. and Stevens J.. Structures of receptorcomplexes of a northamerican H7N2influenza hemagglutinin with a loop deletion in thereceptor binding site[J]. PLoS Pathogens,2010,6(90): e1001081.
Yang P., Bansal A., Liu C. and Air G. M.. Hemagglutinin specificity and neuraminidasecoding capacity of neuraminidase-deficient influenza viruses[J]. Virology,1997,229(1):155-165.
Yao M., Zhang X., Gao J., Chai T., Miao Z., Ma W., Qin M., Li Q., Li X., Liu J. and Zhang H..The occurrence and transmission characteristics of airborne H9N2avian influenzavirus[J]. Berl Munch Tierarztl Wochenschr,2011,124(3-4):136-141.
Ye Q., Chen B., Tong Z., Nakamura S., Sarria R., Costabel U. and Guzman J.. Thalidomidereduces IL-18, IL-8and TNF-alpha release from alveolar macrophages in interstitial lungdisease[J]．Eur Respir J,2006,28:824-831.
Zhao C., Hsiang T. Y., Kuo R. L. and Krug R. M.. ISG15conjugation system targets the viralNS1protein in influenza A virus infected cells. Proc Natl Acad Sci USA,2010,107(5):2253-2258.
Zheng X., Hong L., Shi L., Guo J., Sun Z. and Zhou J.. Proteomics analysis of host cellsinfected with infectious bursal disease virus[J]. Mol Cell Proteomics,2008,7:612-625.
Zhirnov O. P., Konakova T. E., Wolff T. and Klenk H. D.. NS1protein of influenza A virusdown-regulates apoptosis. J Virol,2002,76(4):1617-1625.
Zhu X., Yu W., McBride R., Li Y., Chen L. M., Donisd R. O., Tong S. X., Paulson J. C. andWilson I. A.. Hemagglutinin homologue from H17N10bat influenza virus exhibitsdivergent receptor-binding and pH-dependent fusion activities. Proc Natl Acad Sci USA,2013,110:1458-1463.
Zhou L., Liao Q., Dong L., Huai Y., Bai T., Xiang N., Shu Y., Liu W., Wang S., Qin P., WangM., Xing X., Lv J., Chen R. Y., Feng Z., Yang W., Uyeki T. M. and Yu H.. Risk factors forhuman illness with avian influenza A (H5N1) virus infection in China[J]. J Infect Dis,2009,199:1726-1734.
Zou W., Ke J., Zhang A., Zhou M., Liao Y., Zhu J., Zhou H., Tu J., Chen H. and Jin M..Proteomics analysis of differential expression of chicken brain tissue proteins in responseto the neurovirulent H5N1avian influenza virus infection[J]. J Proteome Res,2010,9(8):3789-3798.
Zürcher T., Yates P. J., Daly J., Sahasrabudhe A., Walters M., Dash L., Tisdale M. andMcKimm-Breschkin J. L.. Mutations conferring zanamivir resistance in human influenzavirus N2neuraminidases compromise virus fitness and are not stably maintained invitro[J]. J Antimicrob Chemother,2006,58(4):723-732.
陈慰峰.医学免疫学（第四版）[M].北京：人民卫生出版社，2006.
董书伟,荔霞,刘永明,王胜义,王旭荣,刘世祥,齐志明.蛋白质组学研究进展及其在中兽医学中的应用探讨[J].生物技术,2012,39(1):45-49
甘孟侯.禽流感[M].北京：北京农业出版社,2002,1-20.
郭霄峰,廖明,辛朝安. H9N2亚型禽流感病毒的致病特性研究.华南农业大学学报[J],2001,22(7):70-72
梁立滨,赵东明,李俊平,李雁冰,施建忠,姜永萍,陈化兰. H5N1亚型禽流感病毒感染小鼠肺组织蛋白质组分析[J].中国预防兽医学报,2011,33(4):261-264
刘洪雨,刘玉芬,于尔松.禽流感病毒的研究进展[J].畜牧兽医科技信息,2005,1:4.
刘增辉.病理染色技术[M].人民卫生出版社,北京,2000,157–158.
卢占军．感染马立克氏病病毒SPF鸡法氏囊蛋白质组学研究[D].扬州大学，扬州,2009．
吕进,王希良．流感病毒感染介导的免疫病理损伤研究进展[J]．生物化学与生物物理进展,2009,36:961-967．
宋琳莉,孟庆刚．流感病毒诱导宿主细胞凋亡的相关因子研究评述[J]．中华中医药学刊,2008,26:739-741．
韦平,秦爱建.重要动物病毒分子生物学[M].科学出版社,2008,4-5.
Adachi M., Matsukura S., Tokunaga H. and Kokubu F.. Expression of cytokines on humanbronchial epithelial cells induced by influenza virus A[J]. Int Arch Allergy Immunol,1997,113(1-3):307-311.
Akira S., Taga T. and Kishimoto T.. Interleukin-6in biology and medicine[M]. Adv Immunol,1993,54:1-78.
Alexander D. J.. A review of avian influenza in different bird species[J]. Vet Micro biol,2000a,74:3-13.
Alexander D. J. and Brown I. H.. Recent zoonoses caused by influenza A viruses[J]. Rev SciTech,2000b,19:197-125.
Alfonso P., Rivera J., Hernaez B., Alonso C. And Escribano J. M.. Identification of cellularproteins modified in response to African swine fever virus infection by proteomics[J].Proteomics,2004,4:2037-2046.
Andersson T., Johansson M., Bolmsjo G. and James P.. Automating MALDI sample plateloading. J Proteome Res,2007,6(2):894-896.
Aoki F. Y., Boivin G. and Roberts N.. Influenza virus susceptibility and resistance tooseltamivir[J]. Antivir Ther,2007,12:603-616.
Azad N. S., Rasool N., Annunziata C. M., Minasian L., Whiteley G. and Kohn E. C..Proteomics in clinical trials and practice: present uses and future promise[J]. Mol CellProteomics,2006,5:1819-1829.
Banks J., Special E. S., Moore E., Plowright L., Piccirillo A., Capua I., Cordioli P., Fioretti A.and Alexander D. J.. Changes in the haemagglutinin and the neuraminidase genes prior tothe emergence of highly pathogenic H7N1avian influenza viruses in Italy[J]. Arch Virol,2001,146(5):963-973.
Bi J., Deng G., Dong J., Kong F., Li X., Xu Q., Zhang M., Zhao L. and Qiao J.. Phylogeneticand molecular characterization of H9N2influenza isolates from chickens in Northern China from2007-2009[J]. PLoS One,2010,5: e13063.
Bouvier N. M., Lowen A. C. And Palese P.. Oseltamivir-resistant influenza A viruses aretransmitted efficiently among guinea pigs by direct contact but not by aerosol[J]. J Virol,2008,82:10052-10058.
Bright R. A., Medina M. J., Xu X. Y., Perez-Oronoz G., Wallis T. R., Davis X. M., PovinelliL., Cox N. J. and Klimov A. I.. Incidence of adamantance resistance among influenza A(H3N2) virus isolated worldwide from1994to2005: a cause for concern[J]. Lancet,2005,366(9495):1175-1181.
Brown E. G.. Influenza virus genetics. Biomed Phannacother.2000,54(4):196-209.
Brown I. H., Banks J., Manvell R. J., Essen S. C., Shell W., Slomka M., Londt B. andAlexander D.J.. Recent epidemiology and ecology of influenza A viruses in avian speciesin Europe and the Middle East[J]. Dev Biol(Basel),2006,124:45-50.
Butt K. M., Smith G. J., Chen H., Zhang L. J., Leung Y. H., Xu K. M., Lim W., Webster R. G.,Yuen K. Y., Peiris J. S. and Guan Y.. Human infection with an avian H9N2influenza Avirus in Hong Kong in2003[J]. J Clin Microbiol,2005,43:5760-5767.
Capua I., Mutinelli F., Marangon S. and Alexander D. J.. H7N1avian influenza in Italy (1999to2000) in intensively reared chickens and turkeys [J]. Avian Pathol,2000,29(6):537-543.
Cerretti D.P., Kozlosky C.J., Mosley B., Nelson N., Van Ness K., Greenstreet T. A., March C.J., Kronheim S. R., Druck T. and Cannizzaro L. A.. Molecular cloning of the interleukin-1beta converting enzyme[J]. Science,1992,256:97-100.
Chan M. C., Cheung C. Y., Chui W. H., Tsao S. W., Nicholls J. M., Chan Y. O., Chan R. W.,Long H. T., Poon L. L., Guan Y. and Peiris J. S.. Proinflammatory cytokine responsesinduced by influenza A (H5N1) viruses in primary human alveolar and bronchialepithelial cells[J]. Respir Res,2005,6:135
Chan R. W., Yuen K. M., Yu W. C., Ho C. C., Nicholls J. M., Peiris J. S. and Chan M. C..Influenza H5N1and H1N1virus replication and innate immune responses in bronchialepithelial cells are influenced by the state of differentiation[J]. PLoS ONE,2010,5:e8713
Chen W., Calvo P. A., Malide D., Gibbs J., Schubert., Bacik I., Basta S., O'Neill R., Schickli J.,Palese P., Henklein P., Bennink J. R. and Yewdell J. W.. A novel influenza A virusmitochondrial protein that induces cell death[J]. Nat Med,2001,7:1306-1312.
Chien C. Y., Tejero R., Huang Y., Zimmerman D. E., Ríos C. B., Krug R. M. and MontelioneG. T.. A novel RNA-binding motif in influenza A virus non-structural protein1. Nat Struct1997,4(11):891-895.
Choi Y. K., Ozaki H., Webby R. J., Webster R. G., Peiris J. S., Poon L., Butt C., Leung Y. H. C.and Guan Y.. Continuing evolution of H9N2influenza viruses in southeastern China [J]. JVirol,2004,78:8609-8614.
Coleman J. R.. The PB1-F2protein of Influenza A virus: increasing pathogenicity bydisrupting alveolar macrophages[J]. Virol J,2007,4:9.
Colman P. M., Laver W. G., Varqhese J. N., Baker A. T., Tulloch P. A., Air G. M. and WebsterR. G.. Three-dimensional structure of a complex of antibody with influenza virusneuraminidase[J]. Nature,1987,326(6111):358-363.
Concannon C. G., Gorman A. M. and Samali A.. On the role of Hsp27in regulatingapoptosis[J]. Apoptosis,2003,8:61-70.
Connor R. J., Kawaoka Y., Webster R. G. and Paulson J. C.. Receptor specificity in human,avian, and equine H2and H3influenza virus isolates[J]. Virology,1994,205(1):17-23.
Crouch E. and Wright J. R.. Surfactant proteins A and D and pulmonary host defense[J]. AnnuRev Physiol.2001;63:521-554.
Dairaghi D. J., Soo K. S., Oldham E. R., Premack B. A., Kitamura T., Bacon K. B. and SchallT. J.. RANTES-induced T cell activation correlates with CD3expression[J]. J Immunol,1998,160:426–433
Dawood F. S., Jain S., Finelli L., Shaw M. W., Lindstrom S., Garten R. J., Gubareva L. V., XuX., Bridges C. B. and Uyeki T. M.. Emergence of a novel swine-origin influenza A(H1N1) virus in humans[J]. N Engl J Med,2009,360(25):2605-2615.
de Jong M. D., Simmons C. P., Thanh T. T., Hien V. M., Smith G. J., Chau T. N., Hoang D. M.,Chau N. V., Khanh T. H., Dong V. C., Qui P. T., Cam B. V., Ha do Q., Guan Y., Peiris J. S.,Chinh N. T., Hien T. T. and Farrar J.. Fatal outcome of human influenza A (H5N1) isassociated with high viral load and hyper cytokinemia[J]. Nat Med,2006,12:1203-1207.
Dea S., Bilodeau R., Sauvagcau R., Montpetit C. and Martineau G. P.. Antigenic variant ofswine influenza virus causing proliferative and necrotizing pneumonia in pigs[J]. J VetDiag Invest,1992,4(4):380-392.
Del Prete G., De Carli M., Almerigogna F., Giudizi MG., Biagiotti R. and Romagnani S..Human IL-10is produced by both type1helper (Th1) and type2helper (Th2) T cellclones and inhibits their antigen-specific proliferation and cytokine production[J]. JImmunol,1993,150:353-360.
Dinarello C. A. and Wolff S. M.. The role of interleukin-1in disease[J]. N Engl J Med,1993,328:106-113.
Elster C., Larsen K., Gagnon J., Ruigrok R. W. and Baudin F.. Influenza virus M1proteinbinds to RNA through its nuelear localization signal[J]. J Gen Virol,1997,78(7):1589-1596.
Enelow R., Baramki D. F. and Borish L. C.. Inhibition of effector T lymphocytes mediatedthrough antagonism of IL-4[J]. J Allergy Clin Immunol,2004,113:560-562.
Enserink M. and Kaiser J.. Avian flu finds new mammal hosts[J]. Science,2004,(305):1385.
Fouchier R. A., Schneeberger P. M., Rozendaal F. W., Broekman J. M., Kemink S. A.,Munster V., Kuiken T., Rimmelzwaan G. F., Schutten M., Van Doornum G. J., Koch G.,Bosman A., Koopmans M. and Osterhaus A. D.. Avian influenza A virus (H7N7)associated with human conjunctivitis and a fatal case of acute respiratory distresssyndrome[J]. Proc Natl Acad Sci USA,2004,101(5):1356-1361.
Gabriel Q., Dauber B., Wolff T., Planz O., Klenk H. D. and Stech J.. The viral polymerasemediates adaptation of an avian influenza virus to a mammalian host[J]. Proc Natl AcadSci USA.2005,102(51):18590-18595.
Gambaryan A. S., Piskarev V. E., Yamskov I. A., Sakharov A. M., Tuzikov A. B., Bovin N. V.,Nifant'ev N. E. and Matrosovich M. N.. Human influenza virus recognition ofsialyloligosaccharides[J]. FEBS Lett,1995,366(1):57-60.
Gao G. and Luo H.. The ubiquitin–proteasome pathway in viral infections[J]. Can JPhysiol Pharmacol,2006,84:5-14.
Gao R., Cao B., Hu Y., Feng Z., Wang D. and Hu W.. Human infection with a novel avian-origin influenza A (H7N9) virus[J]. N Engl J Med,2013,368(20):1888-1897.
Gao Y., Zhang Y., Shinya K., Deng G., Jiang Y., Li Z., Gua Y., Tian G., Li Y., Shi J., Liu L.,Zeng X., Bu Z., Xia X., Kawaoka Y. and Chen H.. Identification of amino acids in HAand PB2critical for the transmission of H5N1avian influenza viruses in a mammalianhost[J]. PLoS Pathog,2009,5(12): e1000709.
Garcia-Sastre A.. Inhibition of interferonmediated antiviral responses by influenza A virusesand other negative-strand RNA viruses[J]. Virology,2001,279:375-384.
García-Sastre A., Egorov A., Matassov D., Brandt S., Levy D. E., Durbin J. E., Palese P. andMuster T.. Influenza A virus lacking the NS1gene replicates in interferon-deficientsystems[J]. Virology,1998,252:324-330.
Guo Y. J., Krauss S., Senne D. A., Mo I. P., Lo K. S., Xiong X. P., Norwood M., Shortridge K.F., Webster R. G., Guan Y.. Characterization of the pathogenicity of members of thenewly established H9N2influenza virus lineages in Asia[J]. Virology,2000,267:279-288.
Guo Y., Li J. and Cheng X.. Discovery of men infected by avian influenza A (H9N2) virus[J].Chinese J Exp Clin Virol,1999,13:105-108.
Hammer J. A. and Wu X. S.. Rabs grab motors: defining the connections between RabGTPases and motor proteins[J]. Current Opinion in Cell Biology,2002,14:69-75.
Haria C. and Dennis J. A.. Avian influenza and human health[J]. Acta Tropica,2002,83(1):1-6.
Harvey R. A., Zambon M. and Barday W. S.. Restrixtions to the adaption of influenza A virusH5hemagglutinin to the human host[J]. J Virol,2004,78(1):502-507.
Hatta M., Asano Y., Masunaqa K., Ito T., Okazaki K., Toyoda T., Kawaoka Y., Ishihama A.and Kida H.. Mapping of functional domains on influenza A virus RNA polymerase PB2molecule using monoclonal antibodies[J]. Arch Virol,2000,145(9):1947-1961.
Hatta M., Gao P., Halfmann P. and Kawaoka Y.. Molecular basis for high virulence of HongKong H5N1influenza A viruses[J]. Science,2001,293:1840-1842.
Helenius A.. Unpacking the incoming influenza virus[J]. Cell,1992,69:577-578.
Hillaire M. L., van Trierum S. E., Kreijtz J. H., Bodewes R., Geelhoed-Mieras M. M.,Nieuwkoop N. J., Fouchier R. A., Kuiken T., Osterhaus A. D. and Rimmelzwaan G. F..Cross-protective immunity against influenza pH1N12009viruses induced by seasonalinfluenza A (H3N2) virus is mediated by virus-specific T-cells[J]. J Gen Virol,2011,92:2339-2349.
Horimoto T. and Kawaoka Y.. Influenza: lessons from past pandemics, warnings from currentincidents[J]. Nat Rev Microbiol,2005,3(8):591-600.
Horimoto T., Rivera E., Pearson J., Senne D., Krauss S., Kawaoka Y. and Webster R. G.Origin and molecular changes associated with emergence of a highly pathogenic H5N2influenza virus in Mexico [J]. Virol,1995,213(1):223-230.
Hsiang T. Y., Zhao C. and Krug R. M.. Interferon-induced ISG15conjugation inhibitsinfluenza A virus gene expression and replication in human cells[J]. J Virol,2009,83:5971-5977.
Hulse D. J., Webster R. G., Russell R. J. and Pere D. R.. Molecular determinants within thesurface proteins involved in the pathogenicity of H5N1influenza viruses in chickens[J].J Virol,2004,78(18):9954-9964.
Ito T., Couceiro J. N., Kelm S., Baum L. G., Krauss S., Castrucci M. R., Donatelli I., Kida H.,Paulson J. C., Webster R. G. and Kawaoka Y.. Molecular basis for the generation in pigsof influenza A viruses with pandemic potential[J]. J Virol,1998,72(9):7367-7373.
Ito T. and Kawaoka Y.. Host-range barrier of influenza A viruses[J]. Vet Microbiol,2000,74(1-2):71-75.
Ito T., Suzuki Y., Mitnaul L., Vines A., Kida H. and Kawaoka Y.. Receptor specificity ofinfluenza A viruses correlates with the agglutination of erythrocytes from different animalspecies[J]. Virology,1997,227:493-499.
Jakel A., Reid K. B. and Clack H.. Surfactant protein A(SP-A) binds to phosphatidylserineand competes with annex in V binding on late apoptotic cells[J]. Protein Cell,2010,1(2):188-197．
Jia N., de Vlas S. J., Liu Y. X., Zhang J. S., Zhan L., Dang R. L., Ma Y. H., Wang X. J., Liu T.,Yang G. P., Wen Q. L., Richardus J. H., Lu S., Cao W. C.. Serological reports of humaninfections of H7and H9avian influenza viruses in northern China[J]. J Clin Virol,2009,44:225-229.
Jiao P., Tian G., Li Y., Deng G., Jiang Y., Liu C., Liu W., Bu Z., Kawaoka Y. and Chen H.. Asingle-amino-acid substitution in the NS1protein changes the pathogenicity of H5N1avian influenza viruses in mice[J]. J Virol,2008,82(3):1146-1154.
Jofre-Monseny L., Loboda A., Wagner A. E., Huebbe P., BoeschSaadatmandi C., JozkowiczA., Minihane A. M., Dulak J. and Rimbach G.. Effects of apoE genotype on macrophageinflammation and heme oxygenase-1expression[J]. Biochem Biophys Res Commun,2007,357:319-324.
Juknat A., Pietr M., Kozela E., Rimmerman N., Levy L., Coppola G., Geschwind D.and Vogel Z.. Differential transcriptional profiles mediated by exposure to thecannabinoids cannabidiol and D9-tetrahydrocannabinol in BV-2microglial cells[J]. Br JPharmacol,2012,165:2512-2528.
Julkunen I., Melén K., Nyqvist M., Pirhonen J., Sareneva T. and Matikainen S.. Inflammatoryresponses in influenza A virus infection[J]. Vaccine,2001,19: S32-S37．
Karpuzoglu E. and Ahmed S. A.. Estrogen regulation of nitric oxide and inducible nitric oxidesynthase (iNOS) in immune cells: implications for immunity, autoimmune diseases, andapoptosis[J]. Nitric Oxide,2006,15:177-186.
Kash J. C., Tumpey T. M., Proll S. C., Carter V., Perwitasari O., Thomas M. J., Basler C. F.,Palese P., Taubenberger J. K., García-Sastre A., Swayne D. E. and Katze M.G.. Genomicanalysis of increased host immune and cell death responses induced by1918influenzavirus[J]. Nature,2006,443:578-581.
Kawaguchi A., Naito T. and Nagato K.. Involvement of influenza virus PA subunit inassembly of functional RNA polymerase complexes[J]. J Virol,2005,79(2):732-744.
Kawaoka Y., Krauss S. and Webster R. G.. Avian-to-human transmission of the PB1gene ofinfluenza A viruses in the1957and1968pandemics[J]. J Virol,1989,63(11):4603-4608.
Kayali G., Setterquist S. F., Capuano A. W., Myers K. P., Gill J. S. and Gray G. C.. Testinghuman sera for antibodies against avian influenza viruses: horse RBC hemagglutinationinhibition vs. microneutralization assays[J]. J Clin Virol,2008,43:73-78.
Kimura Y.. Cytokines and chemokines induced by influenza virus infection[J]. Nippon Rinsho,2006,64(10):1822-1827．
King D. J.. Evaluation of different methods of inactivation of Newcastle disease virus andavian influenza virus in egg fluids and serum [J]. Avian Dis,1991,35(3):505-514.
Kishore U., Bernal A. L., Kamran M. F., Saxena S., Singh M., Sarma P. U., Madan T. andChakraborty T.. Surfactant proteins SP-A and SP-D in human health and disease[J]. ArchImmunol Ther Exp (Warsz).2005;53:399-417.
Klenk H. D. and Rott R.. The molecular biology of influenza virus pathogenieity[J]. AdvVirus Res,1988,34:247-281.
Kobasa D., Jones S. M., Shinya K., Kash J. C., Copps J., Ebihara H., Hatta Y., Kim J. H.,Halfmann P., Hatta M., Feldmann F., Alimonti J. B., Fernando L., Li Y., Katze M. G.,Feldmann H. and Kawaoka Y.. Aberrant innate immune response in lethal infection ofmacaques with the1918influenza virus[J]. Nature,2007,445:319-323.
Kobasa D., Takada A., Shinya K., Hatta M., Halfmann P., Theriault S., Suzuki H., NishimuraH., Mitamura K., Sugaya N., Usui T., Murata T., Maeda Y., Watanabe S., Suresh M.,Suzuki T., Suzuki Y., Feldmann H. and Kawaoka Y.. Enhanced virulence of influenza Aviruses with the haemagglutinin of the1918pandemic virus[J]. Nature,2004,431(7009):703-707.
Kogure T., Suzuki T., Takahashi T., Miyamoto D., Hidari K. I., Guo C. T., Ito T., Kawaoka Y.and Suzuki Y.. Human trachea primary epithelial cells express both sialyl(α2-3)Galreceptor for human parainfluenza virus type1and avian influenza viruses, and sialyl(α2-6)Gal receptor for human influenza viruses[J]. Glycoconj J,2006,23:101-106.
Koopmans M., Wilbrink B., Conyn M., Natrop G., van der Nat H., Vennema H, Meijer A, vanSteenbergen J., Fouchier R., Osterhaus A. and Bosman A.. Transmission of H7N7avianinfluenza A virus to human beings during a large outbreak in commercial poultry farms inthe Netherlands[J]. Lancet,2004,363:587-593.
Korteweg C. and Gu J.. Pathology, molecular biology, and pathogenesis of avian influenza A(H5N1) infection in humans[J]. Am J Pathol,2008,172(5):1155-1170.
Kostenko S. and Moens U.. Heat shock protein27phosphorylation: kinases, phosphatases,functions and pathology[J]. Cell Mol Life Sci,2009,66(20):3289-3307.
Krug R. M., Yuan W., Noah D. L. and Latham A. G.. Intracellular warfare between humaninfluenza viruses and human cells: the roles of the viral NS1protein[J]. Virology,2003,309:181-189.
Kuchipudi S. V., Nelli R., White G. A., Bain M., Chang K. C. and Dunham S.. Differences ininfluenza virus receptors in chickens and ducks: Implications for interspeciestransmission[J]. J Mol Genet Med,2009,3(1):143-51.
Labadie K., Dos Santos Afonso E., Rameix-Welti M. A., van der Werf S. and Naffakh N..Host-range determinants on PB2protein of influenza A viruses control the interactionbetween the viral polymerase and nucleoprotein in human cells[J]. Virology,2007,362(2):271-282.
Lee S. J., Kim K. H., Park J. S., Jung J. W., Kim Y. H., Kim S. K., Kim W. S., Goh H. G., KimS. H., Yoo J. S., Kim D. W. and Kim K. P.. Comparative analysis of cell surface proteinsin chronic and acute leukemia cell lines[J]．Biochem Biophys Res Commun,2007:357:620-626．
Lee Y. J., Shin J. Y., Song M. S., Lee Y. M., Choi J. G., Lee E. K., Jeong O. M., Sung H. W.,Kim J. H., Kwon Y. K., Kwon J. H., Kim C. J., Webby R. J., Webster R. G. and Choi Y. K..Continuing evolution of H9influenza viruses in Korean poultry[J].Virology,2007,359:313-323.
Li S., Schulman J., Itamura S. and Palese P.. Glycosylation of neuraminidase determines theneurovirulence of influenza A/WSN/33virus. J Virol,1993,67:6667-6673.
Li X., Qi W., He J., Ning Z., Hu Y., Tian J., Jiao P., Xu C., Chen J., Richt J., Ma W. and LiaoM.. Molecular basis of efficient replication and pathogenicity of H9N2avian influenzaviruses in mice[J]. PLoS One,2012,7(6): e40118.
Li Z., Chen H., Jiao P., Deng G., Tian G., Li Y., Hoffmann E., Webster R. G., Matsuoka Y. andYu K.. Molecular basis of replication of duck H5N1influenza viruses in a mammalianmouse model[J]. J Virol,2005;79:12058-12064.
Liu H., Liu X., Cheng J., Peng D., Jia L. and Huang Y.. Phylogenetic analysis of thehemagglutinin genes of twenty-six avian influenza viruses of subtype H9N2isolated fromchickens in China during1996–2001[J]. Avian Dis,2003,47:116-127.
Liu N., Song W., Wang P., Lee K., Chan W., Chen H, and Cai Z.. Proteomics analysis ofdifferential expression of cellular proteins in response to avian H9N2virus infection inhuman cells[J]. Proteomics,2008,8(9):1851-1858.
Livak K. J. and Schmittgen T. D.. Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the2ΔΔCT Method[J]. Methods,2001,25(4):402-408.
Lowen A. C., Mubareka S., Steel J. and Palese P.. Influenza virus transmission is dependenton relative humidity and temperature[J]. PLoS Path,2007,3(10):1470-1476.
Lowen A. C., Mubareka S., Tumpey T. M., Garcia-Sastre A. and Palese P.. The guinea pig as atransmission model for human influenza viruses[J]. Proc Natl Acad Sci U S A,2006,103:9988-9992.
MacNeill C., Umstead T. M., Phelps D. S., Lin Z.W. and Floros J.. Surfactant protein A, aninnate immune factor, is expressed in the vaginal mucosa and is present in vaginal lavagefluid[J]. Immunology,2004,111:91-99.
Maghazachi A. A., Vujanovic N. L., Herberman R. B. and Hiserodt J. C.. Lymphokine-activated killer cells in rats. IV. Developmental relationships among large agranularlymphocytes, large granular lymphocytes, and lymphokine-activated killer cells[J]. JImmunol,1988,140(8):2846-2852.
Mahalingam S., Friedland J. S., Heise M. T., Rulli N. E., Meanger J., Lidbury B. A..Chemokines and viruses: friends or foes?[J]. Trends Microbiol,2003,11(8):383-391.
Maines T. R., Lu X. H., Erb S. M., Edwards L., Guarner J., Greer P. W., Nguyen D. C.,Szretter K. J., Chen L. M., Thawatsupha P., Chittaganpitch M., Waicharoen S., Nguyen D.T., Nguyen T., Nguyen H. H., Kim J. H., Hoang L. T., Kang C., Phuong L. S., Lim W.,Zaki S., Donis R. O., Cox N. J., Katz J. M. and Tumpey T. M.. Avian influenza (H5N1)viruses isolated from humans in Asia in2004exhibit increased virulence in mammals[J].J Virol,2005,79:11788-11800.
Masuda H., Suzuki H., Oshitani H., Saito R., Kawasaki S., Nishikawa M. and Satoh H..Incidence of amantadine-resistant influenza A viruses in sentinel surveillance sites andnursing homes in Niigata, Japan[J]. Micrebiol Immunol,2000,44(10):833-839.
Matrosovich M. N., Krauss S. and Webster R. G.. H9N2influenza A viruses from poultry inAsia have human virus-like receptor specificity[J]. Virology,2001,281(2):156-162.
Matrosovich M. N., Matrosovich T. Y., Gray T., Roberts N. A. and Hans-Dieter Klenk..Human and avian influenza viruses target different cell types in cultures of human airwayepithelium[J]. Proc Natl Acad Sci USA,2004,101(13):4620-4624.
Matrosovich M. N., Matrosovich T. Y., Gray T., Roberts N. A. and Klenk H. D..Neuraminidase is important for the initiation of influenza virus infection in human airwayepithelium [J]. J Virol,2004,78(22):12665-12667.
Matsukura S., Kokubu F., Noda H., Tokunaga H. and Adachi M.. Expression of IL-6, IL-8,and RANTES on human bronchial epithelial cells, NCI-H292, induced by influenza virusA[J]. J Allergy Clin Immunol,1996,98:1080-1087.
Matsushima-Nishiwaki R., Takai S., Adachi S., Minamitani C., Yasuda E., Noda T., Kato K.,Toyoda H., Kaneoka Y., Yamaguchi A., Kumada T. and Kozawa O.. Phosphorylated heatshock protein27represses growth of hepatocellular carcinoma via inhibition ofextracellular signal-regulated kinase[J]. J Biol Chem,2008,283(27):18852-18860.
Mittal N. and Sanyal S. N.. Exogenous surfactant suppresses inflammation in experimentalendotoxin-induced lung injury[J]. J Environ Pathol Toxicol Oncol,2009,28(4):341-349．
Mumford E., Bishop J., Hendrickx S. and Embarek P. B.. Perdue M Avian influenzaH5N1:risks at the human-animal interface[J]. Food Nutr Bull,2007,28: S357-363.
Muramoto Y., Le T. Q., Phuong L. S., Nguyen T., Nguyen T. H., Sakai-Tagawa Y., HorimotoT., Kida H. and Kawaoka Y.. Pathogenicity of H5N1Influenza A viruses isolated inVietnam between late2003and2005[J]. J Vet Med Sci,2006,68(7):735-737.
Nang N. T., Lee J. S., Song B. M., Kang Y. M., Kim H. S. and Seo S.H.. Induction ofinflammatory cytokines and toll-like receptors in chickens infected with avian H9N2influenza virus[J]. Vet Res,2011,42:64.
Narasimhan J., Potter J. L. and Haas A. L.. Conjugation of the15-kDa interferon-inducedubiquitin homolog is distinct from that of ubiquitin[J]. J Biol Chem,1996,271:324-330.
Nelli R. K., Kuchipudi S. V., White G. A., Perez B. B., Dunham S. P. and Chang K. C..Comparative distribution of human and avian type sialic acid influenza receptors in thepig[J]. BMC Vet Res,2010,6:4.
Nili H. and Asasi K.. Natural cases and an experimental study of H9N2avian influenza incommercial broiler chickens of Iran[J]. Avian Pathol,2002,31(3):247-252.
Ohuchi M., Orlich M., Ohuchi R., Simpson B. E., Garten W., Klenk H. D. and Rott R..Mutations at the cleavage site of the hemagglutinin after the pathogenicity of influenzavirus A/chick/Penn/83(H5N2)[J]. Virology,1989,168(2):274-280.
Osiak A., Utermohlen O., Niendorf S., Horak I. and Knobeloch KP.. ISG15, an interferon-stimulated ubiquitin-like protein, is not essential for STAT1signaling and responsesagainst vesicular stomatitis and lymphocytic choriomeningiti virus[J]. Mol Cell Biol,2005,25:6338-6345.
Ostler T., Davidson W. and Ehl S.. Virus clearance and immunopathology by CD8+T cellsduring infection with respiratory syncytial virus are mediated by IFN-γ[J]． Eur JImmunol,2002,32:2117-2123．
Palese P. and Young J. F.. Variation of influenza A, B, and C viruses[J]. Science1982,(215):1468-1474.
Pandey A. and Mann M.. Proteomics to study genes and genomes[J]. Nature,2000,405(6788):837-846．
Paul W. E. and Ohara J.. B-cell stimulatory factor-1/interleukin4[J]. Annu Rev Immunol,1987,5:429-459
Peiris J. S., de Jong M. D. and Guan Y.. Avian influenza virus(H5N1):a threat to humanhealth[J]. Clin Mierobiol Rev,2007,20:243-267.
Peiris J. S., Yu W. C., Leung C. W., Cheung C. Y., Ng W. F., Nicholls J. M., Ng T. K., Chan K.H., Lai S. T., Lim W. L., Yuen K.Y. and Guan Y.. Re-emergence of fatal human influenzaA subtype H5N1disease[J]. Lancet,2004;363:617-619.
Peiris J. S., Guan Y., Markwell D., Ghose1P., Webster R. G. and Shortridge1K. F..Cocirculation of avian H9N2and contemporary Human H3N2influenza A virus in pigsin Southeastern China: potential for genetic reassortment[J]. J Virol,2001,75(20):9679-9686.
Peiris M., Yuen K. Y., Leung C. W., Chan K. H., Ip P. L., Lai R. W. and Orr W. K.. ShortridgeKF Human infection with influenza H9N2[J]. Lancet,1999,354:916-917.
Pelkmans L., Puntener D. and Helenius A.. Local actin polymerization and dynaminrecruitment in SV40-induced internalization of caveolae[J]. Science,2002,296:535-539.
Perdue M. L. and Suarez D. L.. Structural features of the avian influenza virus hemagglutininthat influence virulence [J]. Vet Microbiol.2000,74(1-2):77-86.
Perdue M. L. and Swayne D. E.. Public health risk from avian influenza virus[J]. Avian Dis,2005,49:317-327.
Perrone L. A., Plowden, J. K., Garcia-Sastre A., Katz, J. M. and Tumpey T. M. H5N1and1918pandemic influenza virus infection results in early and excessive infiltration ofmacrophages and neutrophils in the lungs of mice[J]. PLoS Pathog.2008,4:e1000115
Pertmer T. M., Oran A. E., Moser J. M., Madorin C. A. and Robinson H. L.. DNA vaccinesfor influenza virus: differential effects of maternal antibody on immune responses tohemagglutinin and nucleoprotein[J]. J Virol,2000,74(17):7787-7793.
Pillai S. P. and Lee C. W.. Species and age related differences in the type and distribution ofinfluenza virus receptors in different tissues of chickens, ducks and turkeys[J]. Virol J2010,7:5.
Poon L. M., Pritlove D. C., Fodor E. and Brownlee G. G.. Direct evidence that the Poly(A) tailof influenza A virus is synthesized by reiterative copying of a U track in the virion RNAtemplate[J]. J Virol,1999,73(4):3473-3476.
Qu B., Li X., Gao W., Sun W., Jin Y., Cardona C. J. and Xing Z.. Human intestinal epithelialcells are susceptible to influenza virus subtype H9N2[J]. Virus Res,2012,163:151-159.
Reed L. J. and Muench H.. A simple method of estimating fifty percent endpoints[J]. Am JHyg,1938,27:493-497.
Reid A. H., Fanning T. G., Hultin J. V. and Taubenberger J. K.. Origin and evolution of the1918"Spanish" influenza virus hemagglutinin gene[J]. Proc Natl Acad Sci USA,1999,96(4):1651-1656.
Richard M., Ferraris O., Erny A., Barthélémy M., Traversier A., Sabatier M., Hay A., Lin Y. P.,Russell R. J. and Lina B.. Combinatorial effect of two framework mutations (E119V andI222L) in the neuraminidase active site of H3N2influenza virus on esistance tooseltamivir[J]. Antimicrob Agents Chemother,2011,55(6):2942-2952.
Rogers G. N., Paulson J. C., Daniels R. S., Skehel J. J., Wilson I. A. and Wiley D. C.. Singleamino acid substitutions in influenza haemagglutinin change receptor specificity[J].Nature,1983,304:76-78.
Rogers G. N. and Paulson J. C.. Receptor determinants of human and animal influenza virusisolates: differences in receptor specificity of the H3hemagglutinin based on species oforigin[J]. Virology,1983,127:361-373.
Samji T.. Influenza A: understanding the viral life cycle[J]. Yale J Biol Med,2009,82(4):153-159.
Santis R. D., Faggioni G., Ciammaruconi A., et al. A FRET based melting curve analysis todetect nucleotide variations in HA receptor-binding site of H5N1virus[J]. Mol CellProbes,2010,24(5):298-302.
Seabra M. C., Coudrier E.. Rab GTPases and myosin motors in organelle motility[J]. Traffic,2004,5:393-399.
Shinya K., Ebinal M.,Yamada S., et a1. Influenza virus receptor in the humanairway[J]．Narute,2006,440:435-437.
Shohei K., Ken J. I., Cevayir C., et al. Innate immune response to viral infection[J]. Cytokine,2008,43(3):336-341.
Simonsen L., Clarke M. J., Schonberger L. B., Arden N. H., Cox N. J.,&Fukuda K..Pandemic versus epidemic influenza mortality: a pattern of changing age distribution[J]. JInfect Dis,1998,178(1):53-60.
Skehel J. J., Wiley D. C.. Receptor binding and membrane fusion in virus entry: the influenzahemagglutinin[J]. Annu Rev Biochem,2000,(69):531-569.
Skehel J. J.. Polypeptied synthesis in influenza virus-infected cells[J]. Virology,1972,49:23-36.
Sorrell E. M., Wan H., Araya Y., Song H. and Perez D. R.. Author Affiliations. Minimalmolecular constraints for respiratory droplet transmission of an avian-human H9N2influenza A virus[J]. Proc Natl Acad Sci USA,2009,106(18):7565-7570.
Spittler A., Razenberger M.,Kupper H., Kaul M., Hackl W., Boltz-Nitulescu G., Függer R. andRoth E.. Relationship between interleukin-6plasma concentration in patients with sepsis,monocyte phenotype, monocyte phagocytic properties and cytokine production[J]. ClinInfect Dis,2000,31:1338-1342.
Stegeman A., Bouma A. and Elbers A. R.. Avian influenza A virus (H7N7) epidemic in TheNetherlands in2003: course of the epidemic and effectiveness of control measures[J]. JInfect Dis,2004,190(12):2088-2095.
Steinhauer D. A.. Role of Hemagglutinin Cleavage for the Pathogenieity of InfluenzaVirus[J].Virology,1999,258: l-20.
Stevens J., Blixt O., Tumpey T. M., Taubenberger J. K., Paulson J. C. and Wilson I. A..Structure and receptor specificity of the hemagglutinin from an H5N1influenza virus[J].Science,2006,312:404-410.
Stolp B. and Fackler O. T.. How HIV Takes Advantage of the Cytoskeleton in Entry andReplication[J]. Viruses-Basel,2011,3:293-311.
Subbarao E. K., London W. and Murphy B. R.. A single amino acid in the PB2gene ofinfluenza A virus is a determinant of host range[J]. J Virol,1993,67(4):1761-1764.
Sun K. and Metzger D. W.. Inhibition of pulmonary antibacterial defense by interferon-γduring recovery from influenza infection[J]．Nat Med,2008,14:558-564.
Suzuki Y., Ito T., Suzuki T., Holland R. E., Chambers T. M., Kiso M., Ishida H. and KawaokaY.. Sialic acid species as a determinant of the host range of influenza A viruses[J]. J Virol,2000,74:11825-11831.
Tarendeau F., Boudet J., Guilligay D., Mas P. J., Bougault C. M., Boulo S., Baudin F.,Ruigrok R. W., Daigle N., Ellenberg J., Cusack S., Simorre J. P. and Hart D. J.. Structureand nuclear import function of the C-terminal domain of influenza virus polymerase PB2subunit[J]. Nature,2007,14(3):229-233.
Tong A., Wu L., Lin Q., Lau Q. C., Zhao X., Li J., Chen P., Chen L., Tang H., Huang C. andWei Y. Q.. Proteomic analysis of cellular protein alterations using a hepatitis B virus-producing cellular model[J]. Proteomics,2008,8:2012-2023
Twu K. Y., Kuo R. L., Marklund J. and Krug R. M.. The H5N1influenza virus NS genesselected after1998enhance virus replication in mammalian cells[J]. J Virol,2007,81(15):8112-8121.
Bremner K. H., Scherer J., Yi J. L., Vershinin M., Gross S. P. and Vallee R. B.. Adenovirustransport via direct interaction of cytoplasmic dynein with the viral capsid hexonsubunit[J]. Cell Host Microbe,2009,6:523-535.
Van Reeth K.. Cytokines in the pathogenesis of influenza. Vet Microbiol.2000;74:109-116.
Van Snick J.. Interleukin-6: an overview[J]. Annu Rev Immunol,1990,8:253-278.
Vester D., Rapp E., Gade D., Genzel Y. and Reichl U.. Quantitative analysis of cellularproteome alterations in human influenza A virus-infected mammalian cell lines[J].Proteomics,2009,9(12):3316-3327.
Vey M., Orlich M., Adler S., Klenk H. D., Rott R. and Garten W.. Hemagglutinin activationof pathogenic avian viruses of serotype H7requires the protease recognition motif R-X-K/R-R [J]. Virology,188(1):408-413.
Viswanathan K., Koh X., Chandrasekaran A., Pappas C., Raman R., Srinivasan A., Shriver Z.,Tumpey T. M. and Sasisekharan R.. Determinants of glycan receptor specificity of H2N2influenza A virus hemagglutinin[J]. PLoS ONE,2010,5(10): e13768.
Wan H. and Perez D. R.. Quail carry sialic acid receptors compatible with binding of avianand human influenza viruses[J]. Virology,2006,346(2):278-286.
Wang M., Fu C. X. and Zheng B. J.. Antibodies against H5and H9avian influenza amongpoultry workers in China[J]. N Engl J Med,2009,360:2583-2584
Wasinger V. C., Cordwell S. J., Cerpa-Poljak A., Yan J. X., Gooley A. A., Wilkins M. R.,Duncan M. W., Harris R., Williams K. L. and Humphery-Smith I.. Progress with gene-product mapping of the Mollicutes: Mycoplasma genitalium[J]. Electrophoresis,1995,16:1090-1094.
Watanabe K., Fuse T., Asano I., Tsukahara F., Maru Y., Nagata K., Kitazato K. and KobayashiN.. Identification of Hsc70as an influenza virus matrix protein (M1) binding factorinvolved in the virus life cycle[J]. FEBS Lett,2006,580:5785-5790.
Webster R. G., Air G. M., Metzger D. W., Colman P. M., Varghese J. N., Baker A. T. and LaverW. G. Antigenic structure and variation in an influenza virus N9neuraminidase [J]. JVirol,1987,61(9):2910-2916.
Webster R. G. and Laver W. G. The origin of pandemic influenza [J]. Bull World Health Organ,1972,47(4):449-452.
Webster R. G., Bean W. J., Gorman O. T., Chambers T. M. and Kawaoka Y.. Evolution andecology of influenza A viruses[J]. Microbiol Rev,1992,56(1):152-179.
Webster R. G. and Laver W. G.. The origin of pandemic influenza[J]. Bull World Health Organ,1972,47(4):449-452.
Webster R. G., Yakhno M., Hinshaw V. S., Bean W. J. and Murti K. G. Intestinal influenza:replication and characterization of influenza viruses in ducks [J]. Virology,1978,84(2):268-278.
WHO. Cumulative Number of Confirmed Human Cases of Avian Influenza A/(H5N1)Reported to WHO. Geneva: WHO,2008.
Wong S. S. and Yuen K. Y.. Avian influenza virus infections in humans[J]. Chest,2006,129:156-168.
Wu R., Kausar H., Johnson P., Montoya-Durango D. E., Merchant M. and Rane M. J.. Hsp27regulates Akt activation and polymorphonuclear leukocyte apoptosis by scaffolding MK2to Akt signal complex[J]. J Biol Chem,2007,282(30):21598-21608.
Xing Z., Harper R., Anunciacion J., Yang Z., Gao W., Qu B., Guan Y. and Cardona C. J.. Hostimmune and apoptotic responses to avian influenza virus H9N2in humantracheobronchial epithelial cells[J]. Am J Respir Cell Mol Biol,2011,44:24-33.
Xu R. and Wilson I.. Structural characterization of an early fusion intermediate of influenzavirus hemagglutinin[J]. J Virology,2011,85(10):5172-5182.
Yamada S. Y., Suzuki Y. S., Suzuki T. S, Yamada S., Suzuki Y., Suzuki T., Le M. Q., Nidom C.A., Sakai-Tagawa Y., Muramoto Y., Ito M., Kiso M., Horimoto T., Shinya K., Sawada T.,Kiso M., Usui T., Murata T., Lin Y., Hay A., Haire L. F., Stevens D. J., Russell R. J.,Gamblin S. J., Skehel J. J. and Kawaoka Y.. Hemagglutinin mutations responsible for thebinding of H5N1influenza A viruses to human-type receptors[J]. Nature,2006,444(16):378-382.
Yang H., Chen L. M., Carney P. J., Donis R. O. and Stevens J.. Structures of receptorcomplexes of a northamerican H7N2influenza hemagglutinin with a loop deletion in thereceptor binding site[J]. PLoS Pathogens,2010,6(90): e1001081.
Yang P., Bansal A., Liu C. and Air G. M.. Hemagglutinin specificity and neuraminidasecoding capacity of neuraminidase-deficient influenza viruses[J]. Virology,1997,229(1):155-165.
Yao M., Zhang X., Gao J., Chai T., Miao Z., Ma W., Qin M., Li Q., Li X., Liu J. and Zhang H..The occurrence and transmission characteristics of airborne H9N2avian influenzavirus[J]. Berl Munch Tierarztl Wochenschr,2011,124(3-4):136-141.
Ye Q., Chen B., Tong Z., Nakamura S., Sarria R., Costabel U. and Guzman J.. Thalidomidereduces IL-18, IL-8and TNF-alpha release from alveolar macrophages in interstitial lungdisease[J]．Eur Respir J,2006,28:824-831.
Zhao C., Hsiang T. Y., Kuo R. L. and Krug R. M.. ISG15conjugation system targets the viralNS1protein in influenza A virus infected cells. Proc Natl Acad Sci USA,2010,107(5):2253-2258.
Zheng X., Hong L., Shi L., Guo J., Sun Z. and Zhou J.. Proteomics analysis of host cellsinfected with infectious bursal disease virus[J]. Mol Cell Proteomics,2008,7:612-625.
Zhirnov O. P., Konakova T. E., Wolff T. and Klenk H. D.. NS1protein of influenza A virusdown-regulates apoptosis. J Virol,2002,76(4):1617-1625.
Zhu X., Yu W., McBride R., Li Y., Chen L. M., Donisd R. O., Tong S. X., Paulson J. C. andWilson I. A.. Hemagglutinin homologue from H17N10bat influenza virus exhibitsdivergent receptor-binding and pH-dependent fusion activities. Proc Natl Acad Sci USA,2013,110:1458-1463.
Zhou L., Liao Q., Dong L., Huai Y., Bai T., Xiang N., Shu Y., Liu W., Wang S., Qin P., WangM., Xing X., Lv J., Chen R. Y., Feng Z., Yang W., Uyeki T. M. and Yu H.. Risk factors forhuman illness with avian influenza A (H5N1) virus infection in China[J]. J Infect Dis,2009,199:1726-1734.
Zou W., Ke J., Zhang A., Zhou M., Liao Y., Zhu J., Zhou H., Tu J., Chen H. and Jin M..Proteomics analysis of differential expression of chicken brain tissue proteins in responseto the neurovirulent H5N1avian influenza virus infection[J]. J Proteome Res,2010,9(8):3789-3798.
Zürcher T., Yates P. J., Daly J., Sahasrabudhe A., Walters M., Dash L., Tisdale M. andMcKimm-Breschkin J. L.. Mutations conferring zanamivir resistance in human influenzavirus N2neuraminidases compromise virus fitness and are not stably maintained invitro[J]. J Antimicrob Chemother,2006,58(4):723-732.
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |