一株H3N2亚型犬流感病毒的分离鉴定及其生物学特性的研究
摘要
犬流感是由犬流感病毒引起犬的高度接触性传染病。犬流感病毒可以在犬群中传播并引起犬发病死亡,已经报道的犬流感病毒主要包括H3N2和H3N8两个亚型的流感病毒。犬是与人类接触最密切的动物,但是到目前为止,尚不知道犬流感病毒能否感染除犬以外的其他哺乳动物,亦不清楚是否会感染人,所以对犬流感病毒生物学特性的研究有很重要的公共卫生学意义。
本研究从发病死亡藏獒的病料中分离、获得一株H3N2亚型犬流感病毒(ZJH3N2),对该病毒全基因组序列进行了测定。通过与其他H3亚型流感病毒的序列比较,发现该病毒8个基因片段均与韩国(Korea07株)以及我国广东(GD07株)报道的H3N2亚型犬流感病毒高度同源(98%~99%)。
动物回归实验表明,人工感染犬表现为精神沉郁、食欲下降、体温升高和咳嗽等临床症状。组织病理学分析发现肺脏出血、肺泡中有大量的渗出液,呈现急性肺炎的病理变化。组织病毒滴定结果显示肺脏病毒滴度高达10~(4.75)EID_(50)/g。持续观察感染犬发现,该病毒并没有造成实验犬死亡,这表明该病毒对犬的致死能力不强。犬流感病毒传播试验证明该病毒可以通过空气传播,间接接触感染犬第4天开始发病,出现与人工感染犬相同的临床症状和病理变化。
为了解犬流感病毒分离株(ZJH3N2)能否感染其它动物,选择BALB/c小鼠、豚鼠和麻鸭作为动物模型进行人工感染实验。结果显示该病毒对小鼠具有一定致病性,用10~6EID_(50)的病毒经鼻腔感染小鼠后,攻毒后第2天体重就开始下降,病毒分离发现该病毒可以在小鼠鼻腔和肺等呼吸器官中复制,但不能致死感染小鼠;感染豚鼠后,该病毒只能在鼻腔内复制,而不能在肺中复制;人工感染SPF鸡和麻鸭试验表明该病毒不能感染SPF鸡和麻鸭。
本研究分离鉴定了一株H3N2亚型犬流感病毒ZJH3N2,并对其生物学特性进行了系统研究。ZJH3N2与Korea07以及GD07两株H3N2亚型犬流感病毒的序列同源性很高,这些病毒从进化上均来源于禽流感病毒;然而的结果表明,ZJH3N2对犬、小鼠和豚鼠等哺乳动物均具有感染性,而对SPF鸡和麻鸭却丧失了感染能力。因此,本研究不仅为我国犬流感的流行病学研究提供了试验依据,也为今后研究流感病毒的跨越种间屏障感染新宿主的机制提供了新的病毒株和相关动物模型。
Canine influenza is a highly infectious viral disease caused by canine influenza virus belonging to subtype H3N2 and H3N8. Up to now, we don’t know whether human beings and other mammals are infected with canine virus, whose natural hosts, dogs are considered as human being’s closest friend. For the prevention and control of canine influenza, it is important to make clear the biological characteristics of canine influenza virus.
Our studies focused on ZJH3N2, a H3N2 canine influenza virus isolated from a dead Tibetan mastiff bought from a dog exhibition in Zhejiang province, China. We compared the nucleotide sequence of all the eight gene segments of ZJH3N2 with others reference virus in Genebank. The results indicated that the sequence of all eight genes of ZJH3N2 were highly homologous to Korea H3N2 influenza viruses (Korea07) and Guangdong H3N2 influenza viruses (GD07).
Dog infection studies showed that artificially infected dogs appeared same clinical symptoms as naturally infected dogs. All dogs infected showed depression, lost of appetite, high fever and cough. Two dogs were euthanized 4 days post-infection and tissues were collected for histopathological study and viral isolation. The histopathological test showed that lung had obviously inflammatory exudation and hemorrhage. Viral titers in lung tissues got to 10~(4.75)EID_(50)/g. The remaining infected dogs recovered without any treatment. The canine influenza virus could transmit from dog to dog by air and the dogs got fever 4 days post-contact and appeared similar symptoms as infected dogs.
In order to know whether other animals were infected with ZJH3N2. We used BALB/c mice, guinea pig and duck as the animal models. The mice began to lost weight after 2 days infected with 10~6EID_(50) ZJH3N2 virus. ZJH3N2 virus could replicate in the nasal tissue, trachea, and lungs of mice, but did not kill mice. ZJH3N2 virus could replicate in nasal tissue of guinea pig while no virus was recovered from any tissue of ducks 4 days after the animals were infected with 10~6EID_(50) ZJH3N2.
In summary, we isolated and identified an H3N2 canine influenza virus and its biological Characteristics were studied in detail. The result showed that ZJH3N2 virus highly homologous to Korea H3N2 influenza viruses (Korea07) and Guangdong H3N2 influenza viruses(GD07), which were originally come from avian influenza virus. This study also proved that ZJH3N2 could replicate in other mammals besides dogs, but not in ducks. The result complemented the knowledge of epidemiology of canine influenza virus, and supply material and the animal model for the studies of inter-species transmission of influenza virus.
本研究从发病死亡藏獒的病料中分离、获得一株H3N2亚型犬流感病毒(ZJH3N2),对该病毒全基因组序列进行了测定。通过与其他H3亚型流感病毒的序列比较,发现该病毒8个基因片段均与韩国(Korea07株)以及我国广东(GD07株)报道的H3N2亚型犬流感病毒高度同源(98%~99%)。
动物回归实验表明,人工感染犬表现为精神沉郁、食欲下降、体温升高和咳嗽等临床症状。组织病理学分析发现肺脏出血、肺泡中有大量的渗出液,呈现急性肺炎的病理变化。组织病毒滴定结果显示肺脏病毒滴度高达10~(4.75)EID_(50)/g。持续观察感染犬发现,该病毒并没有造成实验犬死亡,这表明该病毒对犬的致死能力不强。犬流感病毒传播试验证明该病毒可以通过空气传播,间接接触感染犬第4天开始发病,出现与人工感染犬相同的临床症状和病理变化。
为了解犬流感病毒分离株(ZJH3N2)能否感染其它动物,选择BALB/c小鼠、豚鼠和麻鸭作为动物模型进行人工感染实验。结果显示该病毒对小鼠具有一定致病性,用10~6EID_(50)的病毒经鼻腔感染小鼠后,攻毒后第2天体重就开始下降,病毒分离发现该病毒可以在小鼠鼻腔和肺等呼吸器官中复制,但不能致死感染小鼠;感染豚鼠后,该病毒只能在鼻腔内复制,而不能在肺中复制;人工感染SPF鸡和麻鸭试验表明该病毒不能感染SPF鸡和麻鸭。
本研究分离鉴定了一株H3N2亚型犬流感病毒ZJH3N2,并对其生物学特性进行了系统研究。ZJH3N2与Korea07以及GD07两株H3N2亚型犬流感病毒的序列同源性很高,这些病毒从进化上均来源于禽流感病毒;然而的结果表明,ZJH3N2对犬、小鼠和豚鼠等哺乳动物均具有感染性,而对SPF鸡和麻鸭却丧失了感染能力。因此,本研究不仅为我国犬流感的流行病学研究提供了试验依据,也为今后研究流感病毒的跨越种间屏障感染新宿主的机制提供了新的病毒株和相关动物模型。
Canine influenza is a highly infectious viral disease caused by canine influenza virus belonging to subtype H3N2 and H3N8. Up to now, we don’t know whether human beings and other mammals are infected with canine virus, whose natural hosts, dogs are considered as human being’s closest friend. For the prevention and control of canine influenza, it is important to make clear the biological characteristics of canine influenza virus.
Our studies focused on ZJH3N2, a H3N2 canine influenza virus isolated from a dead Tibetan mastiff bought from a dog exhibition in Zhejiang province, China. We compared the nucleotide sequence of all the eight gene segments of ZJH3N2 with others reference virus in Genebank. The results indicated that the sequence of all eight genes of ZJH3N2 were highly homologous to Korea H3N2 influenza viruses (Korea07) and Guangdong H3N2 influenza viruses (GD07).
Dog infection studies showed that artificially infected dogs appeared same clinical symptoms as naturally infected dogs. All dogs infected showed depression, lost of appetite, high fever and cough. Two dogs were euthanized 4 days post-infection and tissues were collected for histopathological study and viral isolation. The histopathological test showed that lung had obviously inflammatory exudation and hemorrhage. Viral titers in lung tissues got to 10~(4.75)EID_(50)/g. The remaining infected dogs recovered without any treatment. The canine influenza virus could transmit from dog to dog by air and the dogs got fever 4 days post-contact and appeared similar symptoms as infected dogs.
In order to know whether other animals were infected with ZJH3N2. We used BALB/c mice, guinea pig and duck as the animal models. The mice began to lost weight after 2 days infected with 10~6EID_(50) ZJH3N2 virus. ZJH3N2 virus could replicate in the nasal tissue, trachea, and lungs of mice, but did not kill mice. ZJH3N2 virus could replicate in nasal tissue of guinea pig while no virus was recovered from any tissue of ducks 4 days after the animals were infected with 10~6EID_(50) ZJH3N2.
In summary, we isolated and identified an H3N2 canine influenza virus and its biological Characteristics were studied in detail. The result showed that ZJH3N2 virus highly homologous to Korea H3N2 influenza viruses (Korea07) and Guangdong H3N2 influenza viruses(GD07), which were originally come from avian influenza virus. This study also proved that ZJH3N2 could replicate in other mammals besides dogs, but not in ducks. The result complemented the knowledge of epidemiology of canine influenza virus, and supply material and the animal model for the studies of inter-species transmission of influenza virus.
引文
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何后军,戴益民,付光华,等. 2004.禽流感病毒分子生物学研究进展[J].江西农业大学学报. 2(26): 290~293.
贺晓静,周杰, Mark Bartlem,等. 2009.流感病毒聚合酶PA亚基与PB1多肽复合体的精细三维结构[J].中国基础科学: 59~61.
黄梦,童光志. 2010. A型流感病毒致病性及跨种间传播的分子生物学基础[J].中国动物传染病学报. 4(18): 76~81.
李仁清,鲁宁,邓瑶,等. 2006.流感病毒RNA聚合酶蛋白PB1在小鼠中可诱导亚型间交叉免疫保护[J].中华微生物学和免疫学杂志. 4(26): 322~327.
祁贤. 2006.我国部分地区猪流感病毒分子流行病学及致病性研究[D].南京农业大学博士学位论文. 45~50.
任丽伟,陈强,徐贵江,等. 2009.禽流感病毒神经氨酸酶的研究进展[J].广东畜牧兽医科技. 2(34): 3~6.
萨姆布鲁克J,拉塞尔D W. 2002.分子克隆实验指南[M].科学出版社.第三版: 1564~1565.
宋晓晖,胡旭东,马素芳,等. 2009.动物源性流感病毒与人流感流行[J].科技导报. (19-24): 19~20.
王全英,乔传玲,申之义. 2005.禽流感病毒神经氨酸酶的结构及其生物学功能[J].动物医学进展. 12(26): 40~43.
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何后军,戴益民,付光华,等. 2004.禽流感病毒分子生物学研究进展[J].江西农业大学学报. 2(26): 290~293.
贺晓静,周杰, Mark Bartlem,等. 2009.流感病毒聚合酶PA亚基与PB1多肽复合体的精细三维结构[J].中国基础科学: 59~61.
黄梦,童光志. 2010. A型流感病毒致病性及跨种间传播的分子生物学基础[J].中国动物传染病学报. 4(18): 76~81.
李仁清,鲁宁,邓瑶,等. 2006.流感病毒RNA聚合酶蛋白PB1在小鼠中可诱导亚型间交叉免疫保护[J].中华微生物学和免疫学杂志. 4(26): 322~327.
祁贤. 2006.我国部分地区猪流感病毒分子流行病学及致病性研究[D].南京农业大学博士学位论文. 45~50.
任丽伟,陈强,徐贵江,等. 2009.禽流感病毒神经氨酸酶的研究进展[J].广东畜牧兽医科技. 2(34): 3~6.
萨姆布鲁克J,拉塞尔D W. 2002.分子克隆实验指南[M].科学出版社.第三版: 1564~1565.
宋晓晖,胡旭东,马素芳,等. 2009.动物源性流感病毒与人流感流行[J].科技导报. (19-24): 19~20.
王全英,乔传玲,申之义. 2005.禽流感病毒神经氨酸酶的结构及其生物学功能[J].动物医学进展. 12(26): 40~43.
韦平,秦爱建. 2008.重要动物病毒分子生物学[M].科学出版社.214~225.
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