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Analysis of Simian Immunodeficiency Virus-specific CD8+ T-cells in Rhesus Macaques by Peptide-MHC-I Tetramer Staining
Published on: December 23, 2016
TRIM5 genotypes in cynomolgus monkeys primarily influence inter-individual diversity in susceptibility to
Akatsuki Saito1, Masako Nomaguchi2, Ken Kono3
1Center for Human Evolution Modeling Research, Primate Research Institute, Kyoto University, 41-2 Kanrin, Inuyama, Aichi 484-8506, Japan.
Abstract:
TRIM5α restricts human immunodeficiency virus type 1 (HIV-1) infection in cynomolgus monkey (CM) cells. We previously reported that a TRIMCyp allele expressing TRIM5-cyclophilin A fusion protein was frequently found in CMs. Here, we examined the influence of TRIM5 gene variation on the susceptibility of CMs to a monkey-tropic HIV-1 derivative (HIV-1mt) and found that TRIMCyp homozygotes were highly susceptible to HIV-1mt not only in vitro but also in vivo. These results provide important insights into the inter-individual differences in susceptibility of macaques to HIV-1mt.
Insights
Genetic variations in TRIM5 influence susceptibility to simian immunodeficiency virus infection in cynomolgus monkeys. TRIMCyp homozygotes showed higher susceptibility to HIV-1mt in vitro and in vivo.
Area of Science:
- Primate immunology
- Virology
- Genetics
Background:
- TRIM5α is a key restriction factor against human immunodeficiency virus type 1 (HIV-1) in non-human primates.
- A specific TRIMCyp allele, encoding a TRIM5-cyclophilin A fusion protein, is prevalent in cynomolgus monkeys (CMs).
Purpose of the Study:
- To investigate the impact of TRIM5 gene variations on CM susceptibility to a monkey-tropic HIV-1 derivative (HIV-1mt).
Main Methods:
- Analysis of TRIM5 gene variation in CMs.
- In vitro infection assays with HIV-1mt.
- In vivo assessment of HIV-1mt susceptibility in CMs.
Main Results:
- TRIMCyp homozygotes exhibited significantly higher susceptibility to HIV-1mt.
- This heightened susceptibility was observed in both in vitro and in vivo experimental settings.
- TRIM5 gene variation directly correlates with inter-individual differences in macaque susceptibility to HIV-1mt.
Conclusions:
- TRIM5 gene polymorphism, specifically TRIMCyp homozygosity, confers increased susceptibility to HIV-1mt in cynomolgus monkeys.
- These findings elucidate the genetic basis for differential susceptibility to lentiviral infections in macaques.
- Understanding TRIM5 variation is crucial for non-human primate models of HIV-1 research.
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