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Variation in simian immunodeficiency virus env is confined to V1 and V4 during progression to simian AIDS
J Overbaugh1, L M Rudensey, M D Papenhausen
1Department of Microbiology, University of Washington, Seattle 98195.
Abstract:
We have monitored changes in the simian immunodeficiency virus (SIV) envelope (env) gene in two macaques which developed AIDS after inoculation with a molecular clone of SIV. As the animals progressed to AIDS, selection occurred for viruses with variation in two discrete regions (V1 and V4) but not for viruses with changes in the region of SIV env that corresponds to the immunodominant, V3 loop of human immunodeficiency virus. Within the highly variable domains, the vast majority of nucleotide changes encoded an amino acid change (98%), suggesting that these envelope variants had evolved as a result of phenotypic selection. Analysis of the biological properties of these variants, which have been selected for in the host, may be useful in defining the mechanisms underlying viral persistence and progression to simian AIDS.
Insights
Researchers tracked changes in the simian immunodeficiency virus (SIV) env gene in macaques with AIDS. Selection favored variants in specific SIV env regions (V1 and V4), not the V3 loop, indicating phenotypic selection during disease progression.
Area of Science:
- Virology
- Immunology
- Primate models of infectious disease
Background:
- Simian immunodeficiency virus (SIV) is a lentivirus that serves as a model for human immunodeficiency virus (HIV).
- Understanding SIV env gene evolution is crucial for insights into lentiviral persistence and pathogenesis.
Purpose of the Study:
- To monitor genetic changes in the SIV env gene during the progression to AIDS in macaques.
- To identify specific regions within the SIV env gene under selection pressure in vivo.
Main Methods:
- Longitudinal monitoring of SIV env gene sequences in two macaques that developed AIDS.
- Analysis of nucleotide and amino acid changes within discrete regions of the SIV env gene, including V1, V4, and the V3 loop equivalent.
Main Results:
- Selection favored viral variants with changes in the V1 and V4 regions of the SIV env gene.
- No significant selection was observed for changes in the SIV env region analogous to the HIV V3 loop.
- A high percentage (98%) of nucleotide changes in variable domains encoded amino acid alterations, suggesting strong phenotypic selection.
Conclusions:
- Phenotypic selection drives the evolution of SIV env variants during AIDS progression in macaques.
- Specific variable regions (V1, V4) of the SIV env gene are critical targets for in vivo selection.
- Studying these selected variants can elucidate mechanisms of viral persistence and simian AIDS pathogenesis.