Antigenic Variation during Persistent Lentivirus Infections and Its Simplications for Vaccine Development
During the past decade the role of genetic variation during RNA virus replication has gained increased attention as a strategy for viral persistence. Through mechanisms such as genomic point mutations, recombination, and reassortment of multipartite genomes, RNA viruses are capable of modifying their genetic constitution, often resulting in altered biologic (host cell specificity, pathogenicity) or immunologic properties (Holland et al., 1982). The propensity for variation among animal RNA viruses by mutation is usually attributed to the relatively high infidelity of virus-encoded RNA polymerases that replicate the viral genome. Compared to DNA polymerases that display error rates of 10-8 to 10-11 nucleotide substitutions per site per year, viral RNA polymerases reveal mutation rates of about 10-4 to 10-5. Moreover, the genetic variations introduced during viral RNA replication in the cell cytoplasm tend to accumulate, as RNA polymerases lack the editing and repair functions typically associated with nuclear DNA polymerases. Thus, RNA viruses appear to constitute a highly variable system of genetic information in which nature is constantly experimenting with novel genetic constitutions.
KeywordsPersistent Infection Febrile Episode Equine Infectious Anemia Virus Clinical Episode Infected Horse
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- Ball, J. , Henry, L., Issel, C., and Montelaro, R., Localization of EIAV glycoprotein epitopes using synthetic peptide methodologies, J. Virol., submitted(1989).Google Scholar
- Kono, Y., Hirasawa, K., Fukunaga, Y., and Taniguchi, T., Recrudescence of EIA by treatment with immunosuppressive drugs, Natl. Inst. Anim. Health Q. (Tokyo), 16:8–15 (1976) .Google Scholar
- Kono, Y., Kobayasi, K., and Fukunaga, Y., Antigenic drift of equine infectious anemia virus in chronically infected horses, Arch. Virol., 41:1–10 (1973).Google Scholar
- Kono, Y., Kobayasi, K., and Fukunaga, Y., Immunization of horses against equine infectious anemia (EIA) with an attenuated EIA virus, Natl. Inst. Anim. Health. Q. (Tokyo) , 10:113–122 (1970).Google Scholar
- Ozel, M., Pauli, G., and Gelderblom, H., The organization of the envelope projections of the surface of HIG, Arch. Virol., 100:255–266 (1988).Google Scholar
- Palker, T., Clark, M. Langlois, A. Matthews, T. Weinhold, K., Randall, R. Bolognesi, D. and Haynes, B. Type-specific neutralization of HIV with antibodies to env — encloded synthetic peptides, Proc. Natl. Acad. Sci. USA, 84:2479–2483.Google Scholar
- Payne, S.L., Fang, F. D., Lui, C. P., Dhruva, B., Rwambo, P., Issel, C.J., and Montelaro, R.C., Antigentic variation and lentivirus persistence: Variations in envelope gene sequences during EIAV infection resemble changes reported for sequential isolates of HIV, Virology, 161:321–331 (1987a).PubMedCrossRefGoogle Scholar
- Payne, S., Parekh, B., Montelaro, R.C., and Issel, C.J., Genomic alterations associated with persistent infections by equine infectious anemia virus, a retrovirus, J. Gen. Virol., 65 : 1 395–1399 (1984)Google Scholar
- Payne, S.L., Rushlow, K., Issel, C.J., and Montelaro, R.C., Expression of EIAV env gene fragments in E. coli: Epitope mapping and serological analyses of constant and variable env gene regions, J. Virol., in press. (1989).Google Scholar
- Preston, B.D., Poiest, B., and Loeb, L.A., Fidelity of HIV-1 reverse transcriptase Science 242: 1168–1171 (1988)Google Scholar
- Rusche, J., Javaherian, K., McDanal, C., Petro, J., Lynn, D., Grimaila, R., Langlois, A., Gallo, R., Arthur, L., Fischinger, P., and Bologinesi, D., Antibodies that inhibit fusion of human immunodeficiency virus-infected cells bind a 24-amino acid sequence of the virual envelope, gp120, Proc. Natl. Acad. Sci. USA, 85:3198–3202 (1987)CrossRefGoogle Scholar
- Rwambo, P M., Issel, C.J., Adams, W.V., Hussain, K.A., Miller, M., and Montelaro, R.C., Equine infectious anemia virus (EIAV): Humoral responses of recipient ponies and antigenic variation during persistent infection, Arch. Virol., in press (1989).Google Scholar