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Updated: Jun 21, 2026
Analysis of Simian Immunodeficiency Virus-specific CD8+ T-cells in Rhesus Macaques by Peptide-MHC-I Tetramer Staining
Published on: December 23, 2016
A comparative study of HIV-1 clade C env evolution in a Zambian infant with an infected rhesus macaque during disease
For Yue Tso1, Federico G Hoffmann, Damien C Tully
1Nebraska Center for Virology and the School of Biological Sciences, University of Nebraska-Lincoln, Lincoln, Nebraska 68583-0900, USA.
Objective:
To evaluate whether HIV-1 clade C (HIV-C) envelope variations that arise during disease progression in rhesus macaque model reflect changes that occur naturally in human infection.
Design:
An infant macaque was infected with SHIV-1157i, an R5 tropic clade C SHIV, that expresses a primary HIV-C envelope derived from an infected human infant and monitored over a 5-year period. Genetic variation of the V1-V5 envelope region, which is the main target for humoral immune responses, derived from the infected macaque and infant was examined.
Methods:
The V1-V5 envelope region was cloned and sequenced from longitudinal peripheral blood mononuclear cell samples collected from the infected macaque and infant. Phylogenetic analysis [phylogenetic tree, diversity, divergence, ratio of nonsynonymous (dN) and synonymous substitution (dS) and dN distribution] was performed. Plasma RNA viral load, CD4(+) T-cell count, changes in the length of V1-V5 region, putative N-linked glycosylation site number and distribution were also measured.
Results:
Phylogenetic analysis revealed that changes in the macaque closely reflected those of the infant during disease progression. Similar distribution patterns of dN and hot spots were observed between the macaque and infant. Analysis of putative N-linked glycosylation sites revealed several common variations between the virus populations in the two host species. These variations correlate with decline of CD4 T-cell count in the macaque and might be linked with disease progression.
Conclusion:
SHIV-C infection of macaque is a relevant animal model for studying variation of primary HIV-C envelope during disease progression and could be used to analyze the selection pressures that are associated with those changes.
Insights
This study shows that the simian-human immunodeficiency virus (SHIV) clade C macaque model accurately reflects human immunodeficiency virus (HIV) clade C envelope variations during disease progression, validating its use in research.
Area of Science:
- Virology
- Immunology
- Primate Models
Background:
- Human immunodeficiency virus (HIV) clade C envelope evolution during infection is complex.
- Understanding these variations is crucial for developing effective vaccines and therapies.
- Rhesus macaque models are utilized to study HIV pathogenesis.
Purpose of the Study:
- To determine if HIV-C envelope variations in a rhesus macaque model mirror those in human HIV infection.
- To assess the utility of the macaque model for studying HIV-C envelope dynamics.
Main Methods:
- Infection of an infant macaque with a clade C SHIV expressing a primary HIV-C envelope.
- Longitudinal monitoring over 5 years, including genetic sequencing of the V1-V5 envelope region.
- Phylogenetic analysis, viral load, CD4+ T-cell counts, and glycosylation site analysis.
Main Results:
- Macaque SHIV-C envelope variations closely paralleled those observed in the human infant.
- Similar patterns of nonsynonymous and synonymous substitutions (dN/dS) and evolutionary hotspots were found.
- Common variations in N-linked glycosylation sites correlated with CD4+ T-cell decline.
Conclusions:
- The SHIV-C macaque model is a relevant tool for studying primary HIV-C envelope variation during disease.
- This model can be used to investigate selection pressures driving HIV evolution in vivo.
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