Viral genetic evolution in macaques infected with molecularly cloned simian immunodeficiency virus correlates with the extent of persistent viremia
V M Hirsch1, G Dapolito, A Hahn
1Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, Twinbrook II Facility, Rockville, Maryland 20852, USA. vhirsch@atlas.niaid.nih.gov
Abstract:
Genetic evolution of the simian immunodeficiency virus (SIV) envelope glycoprotein was evaluated in a group of six macaques (Macaca nemestrina) infected with the molecularly cloned, moderately pathogenic SIVsm62d. The extent of envelope evolution was subsequently evaluated within the context of the individual pattern of viremia and disease outcome. Two macaques in this cohort developed AIDS by 1.5 years postinoculation (progressors), whereas the remaining four macaques remained asymptomatic (nonprogressors). Compared with the nonprogressor macaques, the two progressor macaques exhibited higher persistent plasma viremia, higher homologous neutralizing antibody titers, and more extensive mutation and evolution in the V1 region of envelope. Although clearly distinct in each of these parameters from the progressors, the four nonprogressors exhibited more individual variability with respect to the extent of persistent viremia and genetic evolution of the V1 region of envelope. The extent of V1 envelope varied from no apparent V1 evolution in a macaque with good viral containment to extensive evolution in one macaque with persistent viremia. This study underscores the critical role of persistent replication in the genetic evolution of SIV.
Insights
Persistent simian immunodeficiency virus (SIV) replication drives genetic evolution of the SIV envelope glycoprotein, particularly in progressor macaques. Nonprogressors showed varied viral evolution despite good containment.
Area of Science:
- Virology
- Immunology
- Primate Models
Background:
- Simian immunodeficiency virus (SIV) is a lentivirus that infects non-human primates.
- SIV infection in macaques serves as a model for human immunodeficiency virus (HIV) pathogenesis.
- Understanding SIV evolution is crucial for developing effective antiviral strategies.
Purpose of the Study:
- To investigate the genetic evolution of the SIV envelope glycoprotein in macaques.
- To correlate envelope evolution with viremia patterns and disease progression.
- To identify factors influencing SIV genetic diversity.
Main Methods:
- Infection of six macaques (Macaca nemestrina) with SIVsm62d.
- Monitoring of plasma viremia and disease outcome.
- Genetic sequencing and analysis of the SIV envelope V1 region.
- Measurement of homologous neutralizing antibody titers.
Main Results:
- Two progressor macaques developed AIDS, exhibiting higher viremia and more extensive V1 envelope evolution than four nonprogressors.
- Nonprogressor macaques displayed significant individual variability in viremia and V1 envelope genetic evolution.
- Persistent viral replication correlated with increased mutation and evolution in the SIV envelope V1 region.
Conclusions:
- Persistent SIV replication is a critical driver of SIV envelope genetic evolution.
- Individual host responses and viral dynamics significantly influence SIV evolution.
- The V1 region of the SIV envelope is a key site of adaptive evolution during infection.
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