Geographic, Genetic and functional diversity of antiretroviral host factor TRIMCyp in cynomolgus macaque (Macaca fascicularis).

Saito A, Kono K, Nomaguchi M, Yasutomi Y, Adachi A, Shioda T, Akari H, Nakayama EE.

The antiretroviral factor TRIM5 gene-derived isoform, TRIMCyp, was found in at least three species of Old World monkey, rhesus (Macaca mulatta), pig-tailed (Macaca nemestrina), and cynomolgus macaques (Macaca fascicularis). Although the frequency of TRIMCyp has been well studied in rhesus and pig-tailed macaques, the frequency and prevalence of TRIMCyp in the cynomolgus macaque remain to be definitively elucidated. Here, we studied the geographic and genetic diversity of TRIM5α/TRIMCyp in cynomolgus macaques in comparison with their anti-lentiviral activity. We found that the frequency of TRIMCyp in the population in the Philippines was significantly higher than those in Indonesian and Malaysian populations. We also found major and minor haplotypes of cynomolgus macaque TRIMCyp with single nucleotide polymorphisms in the cyclophilin A domain. We then examined the functional significance of the polymorphism in TRIMCyp and demonstrated that the major haplotype of the TRIMCyp suppressed HIV-1 but not HIV-2, while the minor haplotype of TRIMCyp suppressed HIV-2 but not HIV-1. The major haplotype of TRIMCyp did not restrict a monkey-tropic HIV-1 clone NL-DT5R, which contains a capsid with the simian immunodeficiency virus-derived loop between ŚÁ-helices 4 and 5 and the entire vif gene. These results indicate that the polymorphisms of TRIMCyp affect its anti-lentiviral activity. In total, our results in this study will help understanding the genetic background of cynomolgus macaque TRIMCyp and also the host factors composing species barrier of primate lentiviruses.

Journal of General Virology, Nov 23, 2011

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