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Updated: Aug 8, 2026
Analysis of Simian Immunodeficiency Virus-specific CD8+ T-cells in Rhesus Macaques by Peptide-MHC-I Tetramer Staining
Published on: December 23, 2016
Initial characterization of viral sequences from a SHIV-inoculated pig-tailed macaque that developed AIDS
E B Stephens1, S V Joag, D Sheffer
1Department of Microbiology, Molecular Genetics and Immunology, Marion Merrell Dow Laboratory of Viral Pathogenesis, University of Kansas Medical Center, Kansas City 66160-7240, USA.
Abstract:
In this study, we report on the derivation of a pathogenic SIV-HIV chimeric virus (SHIV) and the initial characterization of the viral sequences from the first (macaque PPc) of a series of pig-tailed macaques that developed CD4+ T cell loss and AIDS. Viral genes were amplified by PCR from the brain, lymphoid, and kidney tissues and their sequences compared to the original SHIV used to initiate passages in macaques. Our results show that the vpu gene, which was nonfunctional in the original SHIV, now coded for functional protein in macaque PPc. The tat and rev genes had no consensus changes but the nef gene had 4-5 consensus changes, depending on the tissue examined. The gp 120 gene had the highest number of nucleotide and amino acid substitution rates that varied from 0.64% to 1.44% and 1.17% to 3.71%, respectively, again depending on the tissue examined. These results suggest that a constellation of changes accumulated at the genomic level during the derivation of a SHIV that was pathogenic for pig-tailed macaques.
Insights
Researchers created a pathogenic simian-human immunodeficiency virus (SHIV) that causes AIDS in macaques. Viral gene analysis revealed significant mutations, particularly in the gp120 gene, contributing to its pathogenicity.
Area of Science:
- Virology
- Immunology
- Primate models
Background:
- Simian immunodeficiency virus (SIV) and human immunodeficiency virus (HIV) cause devastating diseases.
- Developing pathogenic viral models is crucial for understanding disease progression and testing interventions.
Purpose of the Study:
- To derive and characterize a pathogenic SIV-HIV chimeric virus (SHIV).
- To analyze viral genetic changes in macaques that developed Acquired Immunodeficiency Syndrome (AIDS).
Main Methods:
- Derivation of a pathogenic SHIV in pig-tailed macaques.
- Amplification of viral genes (vpu, tat, rev, nef, gp120) from macaque tissues using PCR.
- Sequencing and comparative analysis of viral genes against the original SHIV.
Main Results:
- The vpu gene, initially nonfunctional, became functional in the derived SHIV.
- The nef gene exhibited 4-5 consensus changes, varying by tissue.
- The gp120 gene showed the highest substitution rates, with nucleotide and amino acid changes ranging from 0.64% to 1.44% and 1.17% to 3.71%, respectively.
Conclusions:
- A combination of genomic alterations occurred during SHIV derivation.
- These genetic changes contributed to the SHIV's pathogenicity in pig-tailed macaques.
- The study highlights the complex genomic evolution of pathogenic SHIV strains.
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