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.

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.