EIAV FDDV疫苗株免疫马后部分体液免疫指标的监测与表达EIAV受体和荧光素酶报告基因的293细胞系的建立
|
摘要
为了阐明马传贫驴胎皮肤细胞弱毒疫苗株(FDDV11-EIAV)体液免疫在免疫保护中的作用,为其它慢病毒疫苗的设计提供借鉴,将5匹EIAV阴性健康马分为2组,第1组(6#、7#、8#、9#马)接1ml×10-5TCID50马传贫驴胎皮肤细胞弱毒疫苗株(EIAV FDDV11),第2组(5#马)接种1ml没有接毒的驴胎皮肤细胞培养上清作为非免疫对照组。
免疫接种后210的天内,定期采集血清,利用ELISA方法对不同试验马免疫后血清中针对EIAV结构蛋白p26以及囊膜蛋白的抗体进行了检测,通过监测p26以及囊膜蛋白特异性抗体滴度、p26蛋白特异性抗体的亲和力变化、囊膜蛋白特异性抗体亲和力和抗体构象变化,发现该疫苗株免疫马后第3周出现针对p26以及囊膜蛋白的特异性抗体,其抗体滴度的个体差异性较大,但都维持在较低水平;p26以及囊膜蛋白的特异性抗体亲和力虽有波动,但亲和力水平较高;囊膜蛋白特异性抗体的构象指数都在2.0附近波动,表示囊膜蛋白特异性抗体主要为构象性抗体。免疫100天后囊膜蛋白的特异性抗体水平没有大的变化,p26抗体水平非常低,但其抗体亲和力水平却较高。免疫210天后,所有马均用1ml×10-5血清稀释度EIAV强毒辽宁株(EIAV L-21)进行攻击。攻毒前后对每匹马进行体温监测,攻毒后,对照马(5#马)在第10天出现发热,第16天死亡,其它所有免疫马未见体温升高和其它临床症状,说明FDDV11毒株能够产生良好的免疫保护作用。研究表明马传贫驴胎皮肤细胞弱毒疫苗株产生的体液免疫与马传贫致病株感染马后产生的免疫保护中的体液免疫截然不同,暗示体液免疫在EIAV感染马免疫保护中的作用可能需要进一步评价,同时也为其它慢病毒疫苗的设计提供参考。
此外,为了在体外精确、简便地测定马传染性贫血病毒(EIAV)的中和抗体和研究不同毒株与受体亲和性的差异,以真核表达质粒pcDNA3.1+为载体,插入马慢病毒受体1(ELR1)基因、EIAV驴白细胞疫苗株DLA-122前病毒长末端重复序列(LTR)及其下游的萤火虫荧光素酶(Firefly luciferase)基因构建pELR1-LTR-Luc质粒,转染293细胞,建立了ELR1-LTR(293-E)细胞系。该细胞系能稳定表达ELR1基因,并且能在LTR的控制下有条件地促进萤火虫荧光素酶基因的表达。当EIAV和ELR1结合进入细胞增殖时,表达病毒编码的反式激活蛋白(Tat)能反式激活LTR,使萤火虫荧光素酶基因的表达明显增加。用1000TCID50的EIAV驴胎皮肤细胞适应毒株D18V13接种,24h后检测其荧光强度是对照的3.15倍。培养表明,该细胞系传35代其特征未发生改变,确认构建成功。此细胞系接种EIAV驴胎皮肤细胞适应毒株后,间接免疫荧光检测证明了病毒在细胞内的感染。该细胞系的建立为进一步开展EIAV与细胞受体相互作用以及中和抗体评价等的研究奠定了重要基础。
In order to investigate the humoral immune mechanism of the attenuation and protection of donkey embryo-skin cells attenuated equine infectious anemia virus (FDDV-EIAV), In this study, five EIAV-negative horses were randomly divided into two groups, four horses (6#, 7#, 8# and 9#) in Group 1 were inoculated with 1 ml of FDDV-EIAV, one horses (5#) in Group 2 were served unvaccinated control. Within 210 days post-inoculation, seclected horse’s serum and then dected p26 and env-specific antibody, avidity of antibody and env-specific antibody epitope conformation dependence. Found that p26 and env-specific antibody emergerenced after 3 weeks post-inoculation, the titer of p26- and env-specific antibody changed with different horses and the titers were lower. The avidity of p26 and env-specific antibody was unstable, but standed in a high stable. The conformation index of env-specific antibody changede around 2.0, suggested that env-specific antibody was predominantly conformational epitope specificity. After 100 days post-inoculation, the titer of env-specific antibody was still stable, the avidity of p26- specific antibody was high though the titer was low. Seven months post-inoculation, all horses were challenged with EIAV L-21, all EIAV FDDV11 inoculated horses showed no abnormal change post-challengee and control horse experienced episodes of fever 10 days and died 16 days post-challenge, indicating that EIAV FDDV11 can protect horses from attacting by EIAV L-21. The reasech suggest that the humoral immune response to FDDV-EIAV is distinguished to the response to virienct EIAV and should to further reasech the effect of the humoral immune response to EIAV. At same time, the reaseth can serve as the design vaccines to other lentivirus.
To accurately and conveniently detect neutralizing antibodies and receptor binding affinities of different EIAV strains, the cDNA of EIAV receptor, ELR1, was cloned and inserted in an eukaryotic expression vector pcDNA3.1(+). This recombinant plasmid was designated as pELR1. And then, the transcription regulatory region, long terminal repeat (LTR), of an EIAV vaccine strain and a reporter of firefly luciferase gene were tandemly cloned into pELR1. The resultant expression vector, which was designated as pELR1-LTR-Luc, was used to transfect 293 cells. A transfected cell line, ELR1-LTR-Luc (293E), which consistently expressed ELR1 and expressed luciferase under the regulation of LTR was isolated and further characterized. EIAV was able to enter ELR1-LTR-Luc (293E) cells by binding to ELR1 on the cell membrane and to replicate in the cells. The viral trans-activates transcription (Tat) thus trans activated LTR and sharply enhanced the expression of firefly luciferase gene. The luciferase activity in the cell line treated with 1000 TCID50 for 24h was 2.15 folds higher than the activity in untreated cells. The replication of viruses in the ELR1-LTR-Luc (293E) cells by inoculated with EIAV vaccine strain FDDV was verified by IFA. The tranfected genes in ELR1-LTR-Luc (293E) were consistently expressed during continuously passing for 35 generations. This cell line can be used to set up valuable systems for further study of interaction between EIAV strains and the receptor, as well as to evaluate neutralizing antibodies raised by EIAV strains.
免疫接种后210的天内,定期采集血清,利用ELISA方法对不同试验马免疫后血清中针对EIAV结构蛋白p26以及囊膜蛋白的抗体进行了检测,通过监测p26以及囊膜蛋白特异性抗体滴度、p26蛋白特异性抗体的亲和力变化、囊膜蛋白特异性抗体亲和力和抗体构象变化,发现该疫苗株免疫马后第3周出现针对p26以及囊膜蛋白的特异性抗体,其抗体滴度的个体差异性较大,但都维持在较低水平;p26以及囊膜蛋白的特异性抗体亲和力虽有波动,但亲和力水平较高;囊膜蛋白特异性抗体的构象指数都在2.0附近波动,表示囊膜蛋白特异性抗体主要为构象性抗体。免疫100天后囊膜蛋白的特异性抗体水平没有大的变化,p26抗体水平非常低,但其抗体亲和力水平却较高。免疫210天后,所有马均用1ml×10-5血清稀释度EIAV强毒辽宁株(EIAV L-21)进行攻击。攻毒前后对每匹马进行体温监测,攻毒后,对照马(5#马)在第10天出现发热,第16天死亡,其它所有免疫马未见体温升高和其它临床症状,说明FDDV11毒株能够产生良好的免疫保护作用。研究表明马传贫驴胎皮肤细胞弱毒疫苗株产生的体液免疫与马传贫致病株感染马后产生的免疫保护中的体液免疫截然不同,暗示体液免疫在EIAV感染马免疫保护中的作用可能需要进一步评价,同时也为其它慢病毒疫苗的设计提供参考。
此外,为了在体外精确、简便地测定马传染性贫血病毒(EIAV)的中和抗体和研究不同毒株与受体亲和性的差异,以真核表达质粒pcDNA3.1+为载体,插入马慢病毒受体1(ELR1)基因、EIAV驴白细胞疫苗株DLA-122前病毒长末端重复序列(LTR)及其下游的萤火虫荧光素酶(Firefly luciferase)基因构建pELR1-LTR-Luc质粒,转染293细胞,建立了ELR1-LTR(293-E)细胞系。该细胞系能稳定表达ELR1基因,并且能在LTR的控制下有条件地促进萤火虫荧光素酶基因的表达。当EIAV和ELR1结合进入细胞增殖时,表达病毒编码的反式激活蛋白(Tat)能反式激活LTR,使萤火虫荧光素酶基因的表达明显增加。用1000TCID50的EIAV驴胎皮肤细胞适应毒株D18V13接种,24h后检测其荧光强度是对照的3.15倍。培养表明,该细胞系传35代其特征未发生改变,确认构建成功。此细胞系接种EIAV驴胎皮肤细胞适应毒株后,间接免疫荧光检测证明了病毒在细胞内的感染。该细胞系的建立为进一步开展EIAV与细胞受体相互作用以及中和抗体评价等的研究奠定了重要基础。
In order to investigate the humoral immune mechanism of the attenuation and protection of donkey embryo-skin cells attenuated equine infectious anemia virus (FDDV-EIAV), In this study, five EIAV-negative horses were randomly divided into two groups, four horses (6#, 7#, 8# and 9#) in Group 1 were inoculated with 1 ml of FDDV-EIAV, one horses (5#) in Group 2 were served unvaccinated control. Within 210 days post-inoculation, seclected horse’s serum and then dected p26 and env-specific antibody, avidity of antibody and env-specific antibody epitope conformation dependence. Found that p26 and env-specific antibody emergerenced after 3 weeks post-inoculation, the titer of p26- and env-specific antibody changed with different horses and the titers were lower. The avidity of p26 and env-specific antibody was unstable, but standed in a high stable. The conformation index of env-specific antibody changede around 2.0, suggested that env-specific antibody was predominantly conformational epitope specificity. After 100 days post-inoculation, the titer of env-specific antibody was still stable, the avidity of p26- specific antibody was high though the titer was low. Seven months post-inoculation, all horses were challenged with EIAV L-21, all EIAV FDDV11 inoculated horses showed no abnormal change post-challengee and control horse experienced episodes of fever 10 days and died 16 days post-challenge, indicating that EIAV FDDV11 can protect horses from attacting by EIAV L-21. The reasech suggest that the humoral immune response to FDDV-EIAV is distinguished to the response to virienct EIAV and should to further reasech the effect of the humoral immune response to EIAV. At same time, the reaseth can serve as the design vaccines to other lentivirus.
To accurately and conveniently detect neutralizing antibodies and receptor binding affinities of different EIAV strains, the cDNA of EIAV receptor, ELR1, was cloned and inserted in an eukaryotic expression vector pcDNA3.1(+). This recombinant plasmid was designated as pELR1. And then, the transcription regulatory region, long terminal repeat (LTR), of an EIAV vaccine strain and a reporter of firefly luciferase gene were tandemly cloned into pELR1. The resultant expression vector, which was designated as pELR1-LTR-Luc, was used to transfect 293 cells. A transfected cell line, ELR1-LTR-Luc (293E), which consistently expressed ELR1 and expressed luciferase under the regulation of LTR was isolated and further characterized. EIAV was able to enter ELR1-LTR-Luc (293E) cells by binding to ELR1 on the cell membrane and to replicate in the cells. The viral trans-activates transcription (Tat) thus trans activated LTR and sharply enhanced the expression of firefly luciferase gene. The luciferase activity in the cell line treated with 1000 TCID50 for 24h was 2.15 folds higher than the activity in untreated cells. The replication of viruses in the ELR1-LTR-Luc (293E) cells by inoculated with EIAV vaccine strain FDDV was verified by IFA. The tranfected genes in ELR1-LTR-Luc (293E) were consistently expressed during continuously passing for 35 generations. This cell line can be used to set up valuable systems for further study of interaction between EIAV strains and the receptor, as well as to evaluate neutralizing antibodies raised by EIAV strains.
引文
[1]Van Regenmortel M.H., Mayo M.A., Fauquet C.M., Maniloff J., Virus nomenclature: consensus versus chaos, Arch. Virol. 145 (2000)2227–2232.
[2]Ligné M., Mémoire et observations sur une maladie de sang, connue sous le nom d'anhémie hydrohémie, cachexie acquise du cheval, Rec. Med. Vet. Ec. Alfort 1843(1843) 30–44.
[3]Vallée H., Carré H., Sur la nature infectieuse de l'anémie du cheval, C. R. Acad. Sci. 139 (1904) 331–333.
[4]Rous P., A sarcoma of the fowl transmissible by an agent separable from the tumor cells, J. Exp. Med. 13 (1911) 397–411.
[5]Foil L.D., Meek C.L., Adams W.V., Issel C.J.,Mechanical transmission of equine infectiousanemia virus by deer flies (Chrysops flavidus)and stable flies (Stomoxys calcitrans), Am. J.Vet. Res. 44 (1983) 155–156.
[6]Foil L.D., Adams W.V., McManus J.M., Issel C.J., Bloodmeal residues on mouthparts ofTabanus fuscicostatus (Diptera: Tabanidae) and the potential for mechanical transmissionof pathogens, J. Med. Entomol. 24 (1987)613–616.
[7]Malmquist W.A., Barnett D., Becvar C.S., Production of equine infectious anemia antigen in a persistently infected cell line, Arch. Gesamte Virusforsch. 42 (1973) 361–370.
[8]Baoshan Zhang, Sha Jin, Jing Jin, Feng Li, and Ronald C. Montelaro .A tumor necrosis factor receptor family protein serves as a cellular receptor for the macrophage-tropic equine lentivirus[J].Proc Natl Acad Sci USA,2005,102:9918-9923.
[9]Kawakami, T., L. Sherman, J. Dahlbery, A. Gazit, A. Yaniv, S. R. Tromick, S. A. Aroson. 1987. Nucleotide sequence analysis of equine infectious anemia virus proviral DNA. Virology 158: 300-312.
[10]Rice, N. R., A. Lequarre, J. W. Casey, S. Lahn, R. M. Stephens, and J. Edwards. 1989. Viral DNA in horses infected with equine infectious anemia virus. J. Virol. 63:5194-5200.
[11]Chong, Y. -H., J. M. Ball, C. J. Issel, R. C. Montelaro, and K. E. Rushlow. 1991. Analysis of equine humoral immune responses to the transmembrane envelope glycoprotein (gp45) of equine infectious anemia virus. 65:1013-1018。
[12]Noiman S., Yaniv A., Sherman L., Tronick S.R., Gazit A., Pattern of transcription of the genome of equine infectious anemia virus, J.Virol. 64 (1990) 1839–1843.
[13]Hussain K.A., Issel C.J., Rwambo P.M., Arnizaut A.B., Ball J.M., Schnorr K.L., Montelaro R.C., Identification of gag precursor of equine infectious anaemia virus with monoclonal antibodies to the major viral core protein, p26, J. Gen. Virol. 69 (1988) 1719–1724.
[14]Stephens R.M., Casey J.W., Rice N.R., Equine infectious anemia virus gag and pol genes: relatedness to visna and AIDS virus, Science 231 (1986) 589–594
[15]Stephens, R. M., J. W. Casey, N. R. Rice. 1986. Equine infectious anemia virus gag and pol genes: relatedness to Visna and AIDS virus. Science 231: 589-594.
[16]Veronese, P. D. M., T. D. Copeland, S. Oroszlan, R. C. Gallo, and M. G. Sarngadharan. 1988. Biochemical and immunological analysis of human immunodeficiency virus gag gene products p17 and p24. J. Virol. 62:795-801.
[17]Leroux, C., C. J. Issel, and R. C. Montelaro. 1997. Novel and dynamic evolution of equine infectious anemia virus genomic quasispecies associated with sequential disease cycles in an experimentally infected pony. J. Virol. 71: 9627-9639.
[18]Dawson, L., and X. -F. Yu. 1998. The role of nucleocapsid of HIV-1 in virus assembly. Virology 251, 141-157.
[19]Montelaro, R. C., N. Lohrey, B. Parekh, E. W. Blakeney, and C. J. Issel. 1982. Isolation and comparative biochemical properties of the major internal polypeptides of equine infectious anemia virus. J. Virol. 42:1029-1038.
[20]Rice, N. R., A. Lequarre, J. W. Casey, S. Lahn, R. M. Stephens, and J. Edwards. 1989. Viral DNA in horses infected with equine infectious anemia virus. J. Virol. 63:5194-5200.
[21]Chong, Y. -H., J. M. Ball, C. J. Issel, R. C. Montelaro, and K. E. Rushlow. 1991. Analysis of equine humoral immune responses to the transmembrane envelope glycoprotein (gp45) of equine infectious anemia virus. 65:1013-1018.
[22]潘春刚 1990.博士学位论文,马传染性贫血弱毒分子特性的研究:前病毒中间体 DNA及结构蛋白抗原分析.
[23]王徽 1991.博士学位论文,马传染性贫血强、弱毒蛋白分析及弱毒免疫机制的研究.
[24]Sherman, L., A. Yaniv, H. Lichtman-Pleban, S. R. Tronick, and A. Gazit. 1989. Analysis of regulatory elements of the equine infectious anemia virus and caprine arthritis-encephalitis virus long terminal repeats. J. Virol. 63:4925-4931
[25]Sherman, L., A. Yaniv, H. Lichtman-Pleban, S. R. Tronick, and A. Gazit. 1989. Analysis of regulatory elements of the equine infectious anemia virus and caprine arthritis-encephalitis virus long terminal repeats. J. Virol. 63:4925-4931.
[26]Stephens, R. M., D. Derse, N. R. Rice. 1990. Cloning and characterization of cDNAs encoding equine infectious anemia virus Tat and putative Rev proteins. J. Virol. 64: 3716-3725
[27]Dorn, P., L. DaSilva, L. Martarano, and D. Derse, 1990. Equine infectious anemia virus tat: insight into the structure, function, and evolution of lentivirus trans-activator proteins. J. Virol. 64, 1616-1624
[28]Noiman, S., A. Yaniv, L. Sherman, S. R. Tronick, and A. Gazit. 1990. Pattern of transcription of the genome of equine infectious anemia virus . J. Virol. 64:1839-1343
[29]Derse, D. and S. H. Newbold. 1993. Mutagenesis of EIAV TAT reveals structural features essential for transcriptional activation and TAR element recognition. Virology 194, 530-536
[30]Willbold, D., R. Rosin-Arbestfeld, H. Sticht, R. Frank, and P. Rosch. 1994. Structure of the equine infectious anemia virus Tat protein. Science 264:1584-1587
[31]Carvalho, M., and D. Derse. 1991. Mutational analysis of the equine infectious anemia virus tat-responsive element. J. Virol. 65:3468-3474
[32]Rosin-Arbestfeld, R., D. Willbold, A. Yaniv, and A. Gazit. 1998. The Tat protein of equine infectious anemia virus (EIAV) activates cellular gene expression by read-through transcription. Gene 219:25-35
[33]Madore, S. J. and B. R. Cullen. 1993. Genetic analysis of the cofactor requirement for human immunodeficiency virus type 1 Tat function. J. Virol. 67:3703-3711
[34]Carvalho, M., M. Kirkland, and D. Derse. 1993. Protein interactions with DNA elements in variant equine infectious anemia virus enhancers and their impact on transcriptional activity. J. Virol. 67, 6586-6595
[35]Leroux, C., C. J. Issel, and R. C. Montelaro. 1997. Novel and dynamic evolution of equine infectious anemia virus genomic quasispecies associated with sequential disease cycles in an experimentally infected pony. J. Virol. 71: 9627-9639
[36]Li F., B. A. Puffer, and R. C. Montelaro. 1998. The S2 gene of equine infectious anemia virus is dispensable for viral replication in vitro. J. Virol. 72:8344-8348
[37]Li, F., J. K. Craigo, et al. (2003). A live attenuated equine infectious anemia virus proviral vaccine with a modified S2 gene provides protection from detectable infection by intravenous virulent virus challenge of experimentally inoculated horses. J Virol 77(13): 7244-53.
[38]Jin S, Zhang B, Weisz OA et al. Receptor-mediated entry by equine infectious anemia virus utilizes a pH-dependent endocytic pathway[J]. J Virol ,2005,79(23): 14489-14497.
[39]Brindley, M. A. and W. Maury. Endocytosis and a low-pH step are required for productiveentry of equine infectious anemia virus[J]. J Virol ,2005,79(23): 14482-14488.
[40]Montelaro, R. C., and C. J. Issel. 1990. Immunologic management of equine infectious anemia virus: a model for AIDS vaccine development, p. 221–232. In H. Schellekens and M. C. Horzinek (ed.), Animal models in AIDS. Elsevier Science Publishing, Inc., New York, N.Y.
[41]Perryman, L. E., K. I. O’Rourke, and T. C. McGuire. 1988. Immune responses are required to terminate viremia in equine infectious anemia lentivirus infection. J. Virol. 62:3073–3076.
[42]Kono, Y., H. Sentsui, and Y. Murakami. 1976. Development of specific in vitro lymphocyte stimulation responses in horses infected with equine infectious anemia virus. Vet. Microbiol. 1:31–43.
[43]Swardson, C. J., G. J. Kociba, et al. (1992). Effects of equine infectious anemia virus on hematopoietic progenitors in vitro. Am J Vet Res 53(7): 1176-9.
[44]于力,张秀芳主编.慢病毒和相关疾病.中国农业科技出版社,1996,p205-206.
[45]Hammond, S. A., S. J. Cook, D. L. Lichtenstein, C. J. Issel, and R. C.Montelaro. 1997. Maturation of the cellular and humoral immune responses to persistent infection in horses by equine infectious anemia virus is a complex and lengthy process. J. Virol. 71:3840–3852.
[46]Hammond, S. A., F. Li, et al. (2000). Immune responses and viral replication in long-term inapparent carrier ponies inoculated with equine infectious anemia virus. J Virol 74(13): 5968-81.
[47]Leroux C, Issel CJ, Montelaro RC. Novel and dynamic evolution of equine infectious anemia virus genomic quasispecies associated with sequential disease cycles in an experimentally infected pony.J Virol. 1997 Dec;71(12):9627-39.
[48]Lichtenstein DL, Issel CJ, Montelaro RC. Genomic quasispecies associated with the initiation of infection and disease in ponies experimentally infected with equine infectious anemia virus.J Virol. 1996 Jun;70(6):3346-54.
[49]Payne, S. L., F. -D. Fang, C. -P. Liu, B. R. Dhruva, P. Rwambo, C. J. Issel, and R. C. Montelaro. 1987. Genetic variation and lentivirus persistence: variation in envelope gene sequences during EIAV infection resemble changes reported for sequential isolates of HIV. Virology 161: 321-331.
[50]Zheng YH, Nakaya T, Sentsui H, Kameoka M, Kishi M, Hagiwara K, Takahashi H, Kono Y, Ikuta K. Insertions, duplications and substitutions in restricted gp90 regions of equine infectious anaemia virus during febrile episodes in an experimentally infected horse.J Gen Virol. 1997a Apr; 78 ( Pt 4):807-20.
[51]Zheng YH, Sentsui H, Nakaya T, Kono Y, Ikuta K. In vivo dynamics of equine infectious anemia viruses emerging during febrile episodes: insertions/duplications at the principal neutralizing domain.J Virol. 1997b Jul; 71(7):5031-9.
[52]Leroux C, Issel CJ, Montelaro RC. Novel and dynamic evolution of equine infectious anemia virus genomic quasispecies associated with sequential disease cycles in an experimentally infected pony.J Virol. 1997 Dec; 71(12):9627-39.
[53]Greene WK, Meers J, Fierro G, Carnegie PR, Robinson WF. Extensive sequence variation of feline immunodeficiency virus env genes in isolates from naturally infected cats.Arch Virol. 1993; 133(1-2):51-62.
[54]Suarez DL, Whetstone CA. Identification of hypervariable and conserved regions in the surface envelope gene in the bovine lentivirus. Virology. 1995 Oct 1; 212(2):728-33.
[55]Craigo JK, Leroux C, Howe L, Steckbeck JD, Cook SJ, Issel CJ, Montelaro RC. Transient immune suppression of inapparent carriers infected with a principal neutralizing domain-deficient equine infectious anaemia virus induces neutralizing antibodies and lowers steady-state virus replication.J Gen Virol. 2002 Jun;83(Pt 6):1353-9.
[56]Cook RF, Leroux C, Cook SJ, Berger SL, Lichtenstein DL, Ghabrial NN, Montelaro RC, Issel CJ. Development and characterization of an in vivo pathogenic molecular clone of equine infectious anemia virus.J Virol. 1998 Feb; 72(2):1383-93
[57]McGuire, T. C., K. O'Rourke, W. P. Cheevers. 1987. A review of antigenic variation by the equine infectious anemia virus. Contr. Microbiol. Immunol. 8:77-89
[58]Alkhatib, G., S. -H. Shen, D. Briedis, C. Richardson, B. Massie, R. Weihberg, D. Smith, J. Taylor, E. Paoletti, and J. Roder. 1994. Functional analysis of N-linked glycosylation mutants of the measles virus fusion protein synthesized by recombinant vaccinia virus vectors. J. Virol. 68:1522-1531
[59]Cook RF, Berger SL, Rushlow KE, McManus JM, Cook SJ, Harrold S, Raabe ML, Montelaro RC, Issel CJ. Enhanced sensitivity to neutralizing antibodies in a variant of equine infectious anemia virus is linked to amino acid substitutions in the surface unit envelope glycoprotein.J Virol. 1995 Mar; 69(3):1493-9.
[60]Back, N. K. T., L. Smit, M, Schutten, P. L. Nara, M. Tersmette, and J. Goudsmit. 1993. Mutations in human immunodeficiency virus type 1 gp41 affect sensitivity to neutralization by gp120 antibodies. J. Virol. 67:6897-6902
[61]Fujita, K., J. Silver, and K. Peden. 1992. Changes in both gp120 and gp41 can account for increased growth potential and expended host range of human immunodeficiency virus type 1.J. Virol. 66:4445-4451
[62]Reitter, J. N. and R. C. Desrosiers. 1998. Identification of replication-competent strains of simian immunodeficiency virus lacking multiple attachment sites for N-linked carbohydrates in variable regions 1 and 2 of the surface envelope protein. 72:5399-5407
[63]Ohgimoto, S., T. Shioda, K. Mori, E. E. Nakayama, H. Hu, and Y. Nagai. 1998. Location-specific, unequal contribution of the N glycans in simian immunodeficiency virus gp120 to viral infectivity and removal of multiple glycans without disturbing infectivity. J. Virol. 72:8365-8370
[64]Leonard, C. K., M. W. Spellman, L. Riddle, R. J. Harris, J. N. Thomas, T. J. Gregory, 1990. Assignment of intrachain disulfide bonds and characterization of potential glycosylation sites of the type recombinant immunodeficiency virus envelop glycoprotein (gp120) expressed in Chinese hamster ovary cells. J. Biol. Chem. 265: 10373-10382.
[65]Kawakami, T., L. Sherman, J. Dahlbery, A. Gazit, A. Yaniv, S. R. Tromick, S. A. Aroson. 1987. Nucleotide sequence analysis of equine infectious anemia virus proviral DNA. Virology 158: 300-312
[66]Payne SL, Qi XM, Shao H, Dwyer A, Fuller FJ. Disease induction by virus derived from molecular clones of equine infectious anemia virus.J Virol. 1998 Jan; 72(1):483-7
[67]Perry, S. T., M. T. Flaherty, M. J. Kelly, D. L. Clabough, S. R. Tronick, L. Coggins, L. Whetter, C. R. Lengel, and F. Fuller. 1992. The surface envelope protein gene region of equine infectious anemia virus is not an important determinant of tropism in vitro. J. Virol. 66:4085-4097
[68]Edmonson, P., M. Murphey-corb, L. N. Martin, C. Delahunty, J. Heeney, H. Kornfeld, P. R. Donahue, G. H. Learn, L. Hood, and J. I. Mullins. 1998. Evolution of a simian immunodeficiency virus pathogen. J. Virol. 72:405-415
[69]Marthas, M. L., R. A. Ramos, B. L. Lohman, K. Van Rompay, R. E. Unger, C. J. Miller, B. Banapour, N. C. Pedersen, and P. A. Luciw. 1993. Viral determinants of simian immunodeficiency virus (SIV) virulence in rhesus macaques assessed by using attenuated and pathogenic molecular clones of SIVMAC . J. Virol. 67:6047-6055
[70]Stephen, D., J. E. Embretson, D. C. Anderson, J. I. Mullins, and P. N. Fultz. 1990. Sequence analysis and acute pathogenicity of molecular cloned SIVSMM-PBJ14. Nature 345:636-639
[71]Harrold SM, Cook SJ, Cook RF, Rushlow KE, Issel CJ, Montelaro RC. Tissue sites of persistent infection and active replication of equine infectious anemia virus during acutedisease and asymptomatic infection in experimentally infected equids.J Virol. 2000 Apr;74(7):3112-21
[72]Oaks JL, McGuire TC, Ulibarri C, Crawford TB. Equine infectious anemia virus is found in tissue macrophages during subclinical infection.J Virol. 1998 Sep; 72(9):7263-9
[73]Sellon DC, Perry ST, Coggins L, Wild-type equine infectious anemia virus replicates in vivo predominantly in tissue macrophages, not in peripheral blood monocytes. J Viro, 1992, 66:5906-5913
[74]McGuire TC, Tumas DB, Byrne KM, Hines MT, Leib SR, Brassfield AL, O'Rourke KI, Perryman LE. Major histocompatibility complex-restricted CD8+ cytotoxic T lymphocytes from horses with equine infectious anemia virus recognize Env and Gag/PR proteins.J Virol. 1994 Mar; 68(3):1459-67
[75]Rinaldo C, Huang XL, Fan ZF, Ding M, Beltz L, Logar A, Panicali D, Mazzara G, Liebmann J, Cottrill M, et al.High levels of anti-human immunodeficiency virus type 1 (HIV-1) memory cytotoxic T-lymphocyte activity and low viral load are associated with lack of disease in HIV-1-infected long-term nonprogressors.J Virol. 1995 Sep; 69(9):5838-42
[76]Wei Zhang, David B Auyong, J Lindsay Oaks. Natrual variation of equine infectious anemia virus Gag protein cytotoxic T lymphocyte epitopes. Virology, 1999, 261:242-252
[77]Lonning SM, Zhang W, McGuire TC. Gag protein epitopes recognized by CD4(+) T-helper lymphocytes from equine infectious anemia virus-infected carrier horses.J Virol. 1999b May; 73(5):4257-65
[78]Marthas ML, Sutjipto S, Higgins J, Lohman B, Torten J, Luciw PA, Marx PA, Pedersen NC. Immunization with a live, attenuated simian immunodeficiency virus (SIV) prevents early disease but not infection in rhesus macaques challenged with pathogenic SIV. J Virol. 1990 Aug; 64(8):3694-700
[79]Fagerness, A. J, M. T. Flaherty, et al. (2006). The S2 accessory gene of equine infectious anemia virus is essential for expression of disease in ponies. Virology 349(1): 22-30.
[2]Ligné M., Mémoire et observations sur une maladie de sang, connue sous le nom d'anhémie hydrohémie, cachexie acquise du cheval, Rec. Med. Vet. Ec. Alfort 1843(1843) 30–44.
[3]Vallée H., Carré H., Sur la nature infectieuse de l'anémie du cheval, C. R. Acad. Sci. 139 (1904) 331–333.
[4]Rous P., A sarcoma of the fowl transmissible by an agent separable from the tumor cells, J. Exp. Med. 13 (1911) 397–411.
[5]Foil L.D., Meek C.L., Adams W.V., Issel C.J.,Mechanical transmission of equine infectiousanemia virus by deer flies (Chrysops flavidus)and stable flies (Stomoxys calcitrans), Am. J.Vet. Res. 44 (1983) 155–156.
[6]Foil L.D., Adams W.V., McManus J.M., Issel C.J., Bloodmeal residues on mouthparts ofTabanus fuscicostatus (Diptera: Tabanidae) and the potential for mechanical transmissionof pathogens, J. Med. Entomol. 24 (1987)613–616.
[7]Malmquist W.A., Barnett D., Becvar C.S., Production of equine infectious anemia antigen in a persistently infected cell line, Arch. Gesamte Virusforsch. 42 (1973) 361–370.
[8]Baoshan Zhang, Sha Jin, Jing Jin, Feng Li, and Ronald C. Montelaro .A tumor necrosis factor receptor family protein serves as a cellular receptor for the macrophage-tropic equine lentivirus[J].Proc Natl Acad Sci USA,2005,102:9918-9923.
[9]Kawakami, T., L. Sherman, J. Dahlbery, A. Gazit, A. Yaniv, S. R. Tromick, S. A. Aroson. 1987. Nucleotide sequence analysis of equine infectious anemia virus proviral DNA. Virology 158: 300-312.
[10]Rice, N. R., A. Lequarre, J. W. Casey, S. Lahn, R. M. Stephens, and J. Edwards. 1989. Viral DNA in horses infected with equine infectious anemia virus. J. Virol. 63:5194-5200.
[11]Chong, Y. -H., J. M. Ball, C. J. Issel, R. C. Montelaro, and K. E. Rushlow. 1991. Analysis of equine humoral immune responses to the transmembrane envelope glycoprotein (gp45) of equine infectious anemia virus. 65:1013-1018。
[12]Noiman S., Yaniv A., Sherman L., Tronick S.R., Gazit A., Pattern of transcription of the genome of equine infectious anemia virus, J.Virol. 64 (1990) 1839–1843.
[13]Hussain K.A., Issel C.J., Rwambo P.M., Arnizaut A.B., Ball J.M., Schnorr K.L., Montelaro R.C., Identification of gag precursor of equine infectious anaemia virus with monoclonal antibodies to the major viral core protein, p26, J. Gen. Virol. 69 (1988) 1719–1724.
[14]Stephens R.M., Casey J.W., Rice N.R., Equine infectious anemia virus gag and pol genes: relatedness to visna and AIDS virus, Science 231 (1986) 589–594
[15]Stephens, R. M., J. W. Casey, N. R. Rice. 1986. Equine infectious anemia virus gag and pol genes: relatedness to Visna and AIDS virus. Science 231: 589-594.
[16]Veronese, P. D. M., T. D. Copeland, S. Oroszlan, R. C. Gallo, and M. G. Sarngadharan. 1988. Biochemical and immunological analysis of human immunodeficiency virus gag gene products p17 and p24. J. Virol. 62:795-801.
[17]Leroux, C., C. J. Issel, and R. C. Montelaro. 1997. Novel and dynamic evolution of equine infectious anemia virus genomic quasispecies associated with sequential disease cycles in an experimentally infected pony. J. Virol. 71: 9627-9639.
[18]Dawson, L., and X. -F. Yu. 1998. The role of nucleocapsid of HIV-1 in virus assembly. Virology 251, 141-157.
[19]Montelaro, R. C., N. Lohrey, B. Parekh, E. W. Blakeney, and C. J. Issel. 1982. Isolation and comparative biochemical properties of the major internal polypeptides of equine infectious anemia virus. J. Virol. 42:1029-1038.
[20]Rice, N. R., A. Lequarre, J. W. Casey, S. Lahn, R. M. Stephens, and J. Edwards. 1989. Viral DNA in horses infected with equine infectious anemia virus. J. Virol. 63:5194-5200.
[21]Chong, Y. -H., J. M. Ball, C. J. Issel, R. C. Montelaro, and K. E. Rushlow. 1991. Analysis of equine humoral immune responses to the transmembrane envelope glycoprotein (gp45) of equine infectious anemia virus. 65:1013-1018.
[22]潘春刚 1990.博士学位论文,马传染性贫血弱毒分子特性的研究:前病毒中间体 DNA及结构蛋白抗原分析.
[23]王徽 1991.博士学位论文,马传染性贫血强、弱毒蛋白分析及弱毒免疫机制的研究.
[24]Sherman, L., A. Yaniv, H. Lichtman-Pleban, S. R. Tronick, and A. Gazit. 1989. Analysis of regulatory elements of the equine infectious anemia virus and caprine arthritis-encephalitis virus long terminal repeats. J. Virol. 63:4925-4931
[25]Sherman, L., A. Yaniv, H. Lichtman-Pleban, S. R. Tronick, and A. Gazit. 1989. Analysis of regulatory elements of the equine infectious anemia virus and caprine arthritis-encephalitis virus long terminal repeats. J. Virol. 63:4925-4931.
[26]Stephens, R. M., D. Derse, N. R. Rice. 1990. Cloning and characterization of cDNAs encoding equine infectious anemia virus Tat and putative Rev proteins. J. Virol. 64: 3716-3725
[27]Dorn, P., L. DaSilva, L. Martarano, and D. Derse, 1990. Equine infectious anemia virus tat: insight into the structure, function, and evolution of lentivirus trans-activator proteins. J. Virol. 64, 1616-1624
[28]Noiman, S., A. Yaniv, L. Sherman, S. R. Tronick, and A. Gazit. 1990. Pattern of transcription of the genome of equine infectious anemia virus . J. Virol. 64:1839-1343
[29]Derse, D. and S. H. Newbold. 1993. Mutagenesis of EIAV TAT reveals structural features essential for transcriptional activation and TAR element recognition. Virology 194, 530-536
[30]Willbold, D., R. Rosin-Arbestfeld, H. Sticht, R. Frank, and P. Rosch. 1994. Structure of the equine infectious anemia virus Tat protein. Science 264:1584-1587
[31]Carvalho, M., and D. Derse. 1991. Mutational analysis of the equine infectious anemia virus tat-responsive element. J. Virol. 65:3468-3474
[32]Rosin-Arbestfeld, R., D. Willbold, A. Yaniv, and A. Gazit. 1998. The Tat protein of equine infectious anemia virus (EIAV) activates cellular gene expression by read-through transcription. Gene 219:25-35
[33]Madore, S. J. and B. R. Cullen. 1993. Genetic analysis of the cofactor requirement for human immunodeficiency virus type 1 Tat function. J. Virol. 67:3703-3711
[34]Carvalho, M., M. Kirkland, and D. Derse. 1993. Protein interactions with DNA elements in variant equine infectious anemia virus enhancers and their impact on transcriptional activity. J. Virol. 67, 6586-6595
[35]Leroux, C., C. J. Issel, and R. C. Montelaro. 1997. Novel and dynamic evolution of equine infectious anemia virus genomic quasispecies associated with sequential disease cycles in an experimentally infected pony. J. Virol. 71: 9627-9639
[36]Li F., B. A. Puffer, and R. C. Montelaro. 1998. The S2 gene of equine infectious anemia virus is dispensable for viral replication in vitro. J. Virol. 72:8344-8348
[37]Li, F., J. K. Craigo, et al. (2003). A live attenuated equine infectious anemia virus proviral vaccine with a modified S2 gene provides protection from detectable infection by intravenous virulent virus challenge of experimentally inoculated horses. J Virol 77(13): 7244-53.
[38]Jin S, Zhang B, Weisz OA et al. Receptor-mediated entry by equine infectious anemia virus utilizes a pH-dependent endocytic pathway[J]. J Virol ,2005,79(23): 14489-14497.
[39]Brindley, M. A. and W. Maury. Endocytosis and a low-pH step are required for productiveentry of equine infectious anemia virus[J]. J Virol ,2005,79(23): 14482-14488.
[40]Montelaro, R. C., and C. J. Issel. 1990. Immunologic management of equine infectious anemia virus: a model for AIDS vaccine development, p. 221–232. In H. Schellekens and M. C. Horzinek (ed.), Animal models in AIDS. Elsevier Science Publishing, Inc., New York, N.Y.
[41]Perryman, L. E., K. I. O’Rourke, and T. C. McGuire. 1988. Immune responses are required to terminate viremia in equine infectious anemia lentivirus infection. J. Virol. 62:3073–3076.
[42]Kono, Y., H. Sentsui, and Y. Murakami. 1976. Development of specific in vitro lymphocyte stimulation responses in horses infected with equine infectious anemia virus. Vet. Microbiol. 1:31–43.
[43]Swardson, C. J., G. J. Kociba, et al. (1992). Effects of equine infectious anemia virus on hematopoietic progenitors in vitro. Am J Vet Res 53(7): 1176-9.
[44]于力,张秀芳主编.慢病毒和相关疾病.中国农业科技出版社,1996,p205-206.
[45]Hammond, S. A., S. J. Cook, D. L. Lichtenstein, C. J. Issel, and R. C.Montelaro. 1997. Maturation of the cellular and humoral immune responses to persistent infection in horses by equine infectious anemia virus is a complex and lengthy process. J. Virol. 71:3840–3852.
[46]Hammond, S. A., F. Li, et al. (2000). Immune responses and viral replication in long-term inapparent carrier ponies inoculated with equine infectious anemia virus. J Virol 74(13): 5968-81.
[47]Leroux C, Issel CJ, Montelaro RC. Novel and dynamic evolution of equine infectious anemia virus genomic quasispecies associated with sequential disease cycles in an experimentally infected pony.J Virol. 1997 Dec;71(12):9627-39.
[48]Lichtenstein DL, Issel CJ, Montelaro RC. Genomic quasispecies associated with the initiation of infection and disease in ponies experimentally infected with equine infectious anemia virus.J Virol. 1996 Jun;70(6):3346-54.
[49]Payne, S. L., F. -D. Fang, C. -P. Liu, B. R. Dhruva, P. Rwambo, C. J. Issel, and R. C. Montelaro. 1987. Genetic variation and lentivirus persistence: variation in envelope gene sequences during EIAV infection resemble changes reported for sequential isolates of HIV. Virology 161: 321-331.
[50]Zheng YH, Nakaya T, Sentsui H, Kameoka M, Kishi M, Hagiwara K, Takahashi H, Kono Y, Ikuta K. Insertions, duplications and substitutions in restricted gp90 regions of equine infectious anaemia virus during febrile episodes in an experimentally infected horse.J Gen Virol. 1997a Apr; 78 ( Pt 4):807-20.
[51]Zheng YH, Sentsui H, Nakaya T, Kono Y, Ikuta K. In vivo dynamics of equine infectious anemia viruses emerging during febrile episodes: insertions/duplications at the principal neutralizing domain.J Virol. 1997b Jul; 71(7):5031-9.
[52]Leroux C, Issel CJ, Montelaro RC. Novel and dynamic evolution of equine infectious anemia virus genomic quasispecies associated with sequential disease cycles in an experimentally infected pony.J Virol. 1997 Dec; 71(12):9627-39.
[53]Greene WK, Meers J, Fierro G, Carnegie PR, Robinson WF. Extensive sequence variation of feline immunodeficiency virus env genes in isolates from naturally infected cats.Arch Virol. 1993; 133(1-2):51-62.
[54]Suarez DL, Whetstone CA. Identification of hypervariable and conserved regions in the surface envelope gene in the bovine lentivirus. Virology. 1995 Oct 1; 212(2):728-33.
[55]Craigo JK, Leroux C, Howe L, Steckbeck JD, Cook SJ, Issel CJ, Montelaro RC. Transient immune suppression of inapparent carriers infected with a principal neutralizing domain-deficient equine infectious anaemia virus induces neutralizing antibodies and lowers steady-state virus replication.J Gen Virol. 2002 Jun;83(Pt 6):1353-9.
[56]Cook RF, Leroux C, Cook SJ, Berger SL, Lichtenstein DL, Ghabrial NN, Montelaro RC, Issel CJ. Development and characterization of an in vivo pathogenic molecular clone of equine infectious anemia virus.J Virol. 1998 Feb; 72(2):1383-93
[57]McGuire, T. C., K. O'Rourke, W. P. Cheevers. 1987. A review of antigenic variation by the equine infectious anemia virus. Contr. Microbiol. Immunol. 8:77-89
[58]Alkhatib, G., S. -H. Shen, D. Briedis, C. Richardson, B. Massie, R. Weihberg, D. Smith, J. Taylor, E. Paoletti, and J. Roder. 1994. Functional analysis of N-linked glycosylation mutants of the measles virus fusion protein synthesized by recombinant vaccinia virus vectors. J. Virol. 68:1522-1531
[59]Cook RF, Berger SL, Rushlow KE, McManus JM, Cook SJ, Harrold S, Raabe ML, Montelaro RC, Issel CJ. Enhanced sensitivity to neutralizing antibodies in a variant of equine infectious anemia virus is linked to amino acid substitutions in the surface unit envelope glycoprotein.J Virol. 1995 Mar; 69(3):1493-9.
[60]Back, N. K. T., L. Smit, M, Schutten, P. L. Nara, M. Tersmette, and J. Goudsmit. 1993. Mutations in human immunodeficiency virus type 1 gp41 affect sensitivity to neutralization by gp120 antibodies. J. Virol. 67:6897-6902
[61]Fujita, K., J. Silver, and K. Peden. 1992. Changes in both gp120 and gp41 can account for increased growth potential and expended host range of human immunodeficiency virus type 1.J. Virol. 66:4445-4451
[62]Reitter, J. N. and R. C. Desrosiers. 1998. Identification of replication-competent strains of simian immunodeficiency virus lacking multiple attachment sites for N-linked carbohydrates in variable regions 1 and 2 of the surface envelope protein. 72:5399-5407
[63]Ohgimoto, S., T. Shioda, K. Mori, E. E. Nakayama, H. Hu, and Y. Nagai. 1998. Location-specific, unequal contribution of the N glycans in simian immunodeficiency virus gp120 to viral infectivity and removal of multiple glycans without disturbing infectivity. J. Virol. 72:8365-8370
[64]Leonard, C. K., M. W. Spellman, L. Riddle, R. J. Harris, J. N. Thomas, T. J. Gregory, 1990. Assignment of intrachain disulfide bonds and characterization of potential glycosylation sites of the type recombinant immunodeficiency virus envelop glycoprotein (gp120) expressed in Chinese hamster ovary cells. J. Biol. Chem. 265: 10373-10382.
[65]Kawakami, T., L. Sherman, J. Dahlbery, A. Gazit, A. Yaniv, S. R. Tromick, S. A. Aroson. 1987. Nucleotide sequence analysis of equine infectious anemia virus proviral DNA. Virology 158: 300-312
[66]Payne SL, Qi XM, Shao H, Dwyer A, Fuller FJ. Disease induction by virus derived from molecular clones of equine infectious anemia virus.J Virol. 1998 Jan; 72(1):483-7
[67]Perry, S. T., M. T. Flaherty, M. J. Kelly, D. L. Clabough, S. R. Tronick, L. Coggins, L. Whetter, C. R. Lengel, and F. Fuller. 1992. The surface envelope protein gene region of equine infectious anemia virus is not an important determinant of tropism in vitro. J. Virol. 66:4085-4097
[68]Edmonson, P., M. Murphey-corb, L. N. Martin, C. Delahunty, J. Heeney, H. Kornfeld, P. R. Donahue, G. H. Learn, L. Hood, and J. I. Mullins. 1998. Evolution of a simian immunodeficiency virus pathogen. J. Virol. 72:405-415
[69]Marthas, M. L., R. A. Ramos, B. L. Lohman, K. Van Rompay, R. E. Unger, C. J. Miller, B. Banapour, N. C. Pedersen, and P. A. Luciw. 1993. Viral determinants of simian immunodeficiency virus (SIV) virulence in rhesus macaques assessed by using attenuated and pathogenic molecular clones of SIVMAC . J. Virol. 67:6047-6055
[70]Stephen, D., J. E. Embretson, D. C. Anderson, J. I. Mullins, and P. N. Fultz. 1990. Sequence analysis and acute pathogenicity of molecular cloned SIVSMM-PBJ14. Nature 345:636-639
[71]Harrold SM, Cook SJ, Cook RF, Rushlow KE, Issel CJ, Montelaro RC. Tissue sites of persistent infection and active replication of equine infectious anemia virus during acutedisease and asymptomatic infection in experimentally infected equids.J Virol. 2000 Apr;74(7):3112-21
[72]Oaks JL, McGuire TC, Ulibarri C, Crawford TB. Equine infectious anemia virus is found in tissue macrophages during subclinical infection.J Virol. 1998 Sep; 72(9):7263-9
[73]Sellon DC, Perry ST, Coggins L, Wild-type equine infectious anemia virus replicates in vivo predominantly in tissue macrophages, not in peripheral blood monocytes. J Viro, 1992, 66:5906-5913
[74]McGuire TC, Tumas DB, Byrne KM, Hines MT, Leib SR, Brassfield AL, O'Rourke KI, Perryman LE. Major histocompatibility complex-restricted CD8+ cytotoxic T lymphocytes from horses with equine infectious anemia virus recognize Env and Gag/PR proteins.J Virol. 1994 Mar; 68(3):1459-67
[75]Rinaldo C, Huang XL, Fan ZF, Ding M, Beltz L, Logar A, Panicali D, Mazzara G, Liebmann J, Cottrill M, et al.High levels of anti-human immunodeficiency virus type 1 (HIV-1) memory cytotoxic T-lymphocyte activity and low viral load are associated with lack of disease in HIV-1-infected long-term nonprogressors.J Virol. 1995 Sep; 69(9):5838-42
[76]Wei Zhang, David B Auyong, J Lindsay Oaks. Natrual variation of equine infectious anemia virus Gag protein cytotoxic T lymphocyte epitopes. Virology, 1999, 261:242-252
[77]Lonning SM, Zhang W, McGuire TC. Gag protein epitopes recognized by CD4(+) T-helper lymphocytes from equine infectious anemia virus-infected carrier horses.J Virol. 1999b May; 73(5):4257-65
[78]Marthas ML, Sutjipto S, Higgins J, Lohman B, Torten J, Luciw PA, Marx PA, Pedersen NC. Immunization with a live, attenuated simian immunodeficiency virus (SIV) prevents early disease but not infection in rhesus macaques challenged with pathogenic SIV. J Virol. 1990 Aug; 64(8):3694-700
[79]Fagerness, A. J, M. T. Flaherty, et al. (2006). The S2 accessory gene of equine infectious anemia virus is essential for expression of disease in ponies. Virology 349(1): 22-30.