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Updated: Sep 26, 2026
Analysis of Simian Immunodeficiency Virus-specific CD8+ T-cells in Rhesus Macaques by Peptide-MHC-I Tetramer Staining
Published on: December 23, 2016
Unique pattern of convergent envelope evolution in simian immunodeficiency virus-infected rapid progressor macaques:
Houman Dehghani1, Bridget A Puffer, Robert W Doms
1Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland 20852, USA.
Abstract:
The rate of disease development in simian immunodeficiency virus (SIV) infection of macaques varies considerably among individual macaques. While the majority of macaques inoculated with pathogenic SIV develop AIDS within a period of 1 to 2 years, a minority exhibit a rapid disease course characterized by absence or transience of humoral and cellular immune responses and high levels of virus replication with widespread dissemination of SIV in macrophages and multinucleated giant cells. The goal of this study was to examine viral evolution in three SIVsmE543-3-inoculated rapid progressors to determine the contribution of viral evolution to the development of rapid disease and the effect of the absence of immune pressure upon viral evolution. PCR was used to amplify and clone the entire SIV genome from tissues collected at necropsy, and the course of viral evolution was assessed by env sequences cloned from sequential plasma samples of one rapid progressor (RP) macaque. The majority of sequence changes in RP macaques occurred in the envelope gene. Substitutions were observed in all three animals at specific conserved residues in envelope, including loss of a glycosylation site in V1/V2, a D-to-N/V substitution in a highly conserved GDPE motif, and a P-to-V/H/T substitution in the V3 loop analog. A cell-cell fusion assay revealed that representative env clones utilized CCR5 as a coreceptor, independent of CD4. The selection of specific substitutions in envelope in RP macaques suggests novel selection pressures on virus in such animals and suggests that viral variants that evolve in these animals may play a role in disease progression.
Insights
Viral evolution in rapid progressor macaques with simian immunodeficiency virus (SIV) infection shows specific envelope gene changes. These alterations may drive faster disease progression in the absence of immune pressure.
Area of Science:
- Virology
- Immunology
- Primate models of HIV/AIDS
Background:
- Disease progression in simian immunodeficiency virus (SIV) infection varies significantly among macaques.
- A subset of macaques, termed rapid progressors (RPs), exhibit accelerated disease, characterized by weak immune responses and high viral loads.
Purpose of the Study:
- To investigate viral evolution in SIV-infected rapid progressor macaques.
- To determine the role of viral evolution in rapid disease development.
- To assess the impact of absent immune pressure on viral evolution.
Main Methods:
- Whole genome amplification and cloning of SIV from necropsy tissues.
- Env gene sequencing from sequential plasma samples of a rapid progressor macaque.
- Cell-cell fusion assays to determine coreceptor usage.
Main Results:
- Most sequence changes occurred in the SIV envelope gene in RP macaques.
- Conserved envelope residues, including a V1/V2 glycosylation site and V3 loop analog, were altered.
- Viral env clones utilized CCR5 as a coreceptor, independent of CD4.
Conclusions:
- Specific envelope substitutions in RP macaques suggest unique selection pressures.
- Evolved viral variants may contribute to the rapid progression of SIV-induced disease.
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