J. Virol., Jun 1996, 3346-3354, Vol 70, No. 6
Copyright © 1996, American Society for Microbiology

Genomic quasispecies associated with the initiation of infection and disease in ponies experimentally infected with equine infectious anemia virus

DL Lichtenstein, CJ Issel and RC Montelaro
Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pennsylvania 15261, USA.

Equine infectious anemia virus (EIAV) provides a uniquely dynamic system in which to study the mechanism and role of genomic variation in lentiviral persistence and pathogenesis. We have used a Shetland pony model of infection to investigate the association of specific long terminal repeat (LTR) and env gene genomic sequences with the initiation of infection and the onset of disease. We analyzed viral RNA isolated from a pathogenic stock of virus (EIAV PV) and from plasma taken during the first disease episode from two ponies infected with EIAV PV. Overall sequence variation within gp90 was low in EIAV PV and only slightly higher in plasma virus samples isolated from ponies during the first disease episode. However, a high proportion of mutations were localized to the principal neutralizing domain in EIAV PV and to the principal neutralizing domain and the gp90 hypervariable region in the two pony-derived samples. The rate of fixation of mutations was analyzed and determined to be approximately 4 x 10(-2) mutations per site per year. Sequence diversity within the U3 region of the LTR was extremely low, which suggested that the previously reported hypervariability of this region may be a consequence of selection for replication of EIAV in different host cells. The predominant EIAV PV env and LTR sequences were used to construct chimeric viruses so that the contribution of these sequences to viral pathogenicity could be examined. The chimeras replicated in cultured equine monocytes to the same extent as the parental nonpathogenic virus and did not cause disease in Shetland ponies by 120 days postinfection, suggesting that the EIAV genomic determinants of pathogenesis are complex.

This article has been cited by other articles:

• Craigo, J. K., Zhang, B., Barnes, S., Tagmyer, T. L., Cook, S. J., Issel, C. J., Montelaro, R. C. (2007). Envelope variation as a primary determinant of lentiviral vaccine efficacy. Proc. Natl. Acad. Sci. USA 104: 15105-15110 [Abstract] [Full Text]  
• Craigo, J. K., Li, F., Steckbeck, J. D., Durkin, S., Howe, L., Cook, S. J., Issel, C., Montelaro, R. C. (2005). Discerning an Effective Balance between Equine Infectious Anemia Virus Attenuation and Vaccine Efficacy. J. Virol. 79: 2666-2677 [Abstract] [Full Text]  
• Howe, L., Craigo, J. K., Issel, C. J., Montelaro, R. C. (2005). Specificity of serum neutralizing antibodies induced by transient immune suppression of inapparent carrier ponies infected with a neutralization-resistant equine infectious anemia virus envelope strain. J. Gen. Virol. 86: 139-149 [Abstract] [Full Text]  
• Mealey, R. H., Leib, S. R., Pownder, S. L., McGuire, T. C. (2004). Adaptive Immunity Is the Primary Force Driving Selection of Equine Infectious Anemia Virus Envelope SU Variants during Acute Infection. J. Virol. 78: 9295-9305 [Abstract] [Full Text]  
• Payne, S. L., Pei, X.-f., Jia, B., Fagerness, A., Fuller, F. J. (2004). Influence of Long Terminal Repeat and Env on the Virulence Phenotype of Equine Infectious Anemia Virus. J. Virol. 78: 2478-2485 [Abstract] [Full Text]  
• Howe, L., Leroux, C., Issel, C. J., Montelaro, R. C. (2002). Equine Infectious Anemia Virus Envelope Evolution In Vivo during Persistent Infection Progressively Increases Resistance to In Vitro Serum Antibody Neutralization as a Dominant Phenotype. J. Virol. 76: 10588-10597 [Abstract] [Full Text]  
• Craigo, J. K., Leroux, C., Howe, L., Steckbeck, J. D., Cook, S. J., Issel, C. J., Montelaro, R. C. (2002). 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. 83: 1353-1359 [Abstract] [Full Text]  
• Leroux, C., Craigo, J. K., Issel, C. J., Montelaro, R. C. (2001). Equine Infectious Anemia Virus Genomic Evolution in Progressor and Nonprogressor Ponies. J. Virol. 75: 4570-4583 [Abstract] [Full Text]  
• Cook, R. F., Leroux, C., Cook, S. J., Berger, S. L., Lichtenstein, D. L., Ghabrial, N. N., Montelaro, R. C., Issel, C. J. (1998). Development and Characterization of an In Vivo Pathogenic Molecular Clone of Equine Infectious Anemia Virus. J. Virol. 72: 1383-1393 [Abstract] [Full Text]