title: Geographical, genetic and functional diversity of antiretroviral host factor TRIMCyp in cynomolgus macaque (Macaca fascicularis).
abstract: The antiretroviral factor tripartite motif protein 5 (TRIM5) gene-derived isoform (TRIMCyp) has been found in at least three species of Old World monkey: rhesus (Macaca mulatta), pig-tailed (Macaca nemestrina) and cynomolgus (Macaca fascicularis) macaques. Although the frequency of TRIMCyp has been well studied in rhesus and pig-tailed macaques, the frequency and prevalence of TRIMCyp in cynomolgus macaques remain to be definitively elucidated. Here, the geographical and genetic diversity of TRIM5α/TRIMCyp in cynomolgus macaques was studied in comparison with their anti-lentiviral activity. It was found that the frequency of TRIMCyp in a population in the Philippines was significantly higher than those in Indonesian and Malaysian populations. Major and minor haplotypes of cynomolgus macaque TRIMCyp with single nucleotide polymorphisms in the cyclophilin A domain were also found. The functional significance of the polymorphism in TRIMCyp was examined, and it was demonstrated that the major haplotype of TRIMCyp suppressed human immunodeficiency virus type 1 (HIV-1) but not HIV-2, whilst 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 α-helices 4 and 5 and the entire vif gene. These results indicate that polymorphisms of TRIMCyp affect its anti-lentiviral activity. Overall, the results of this study will help our understanding of the genetic background of cynomolgus macaque TRIMCyp, as well as the host factors composing species barriers of primate lentiviruses.
authors: Primate Research Institute, Kyoto University, Inuyama 484-8506, Japan.
authors: Akatsuki
authors: A
authors: Saito
authors: Department of Viral Infections, Research Institute for Microbial Diseases, Osaka University, Suita 565-0871, Japan.
authors: Ken
authors: K
authors: Kono
authors: Department of Microbiology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8503, Japan.
authors: Masako
authors: M
authors: Nomaguchi
authors: Tsukuba Primate Research Center, National Institute of Biomedical Innovation, Tsukuba 305-0843, Japan.
authors: Yasuhiro
authors: Y
authors: Yasutomi
authors: Department of Microbiology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8503, Japan.
authors: Akio
authors: A
authors: Adachi
authors: Department of Viral Infections, Research Institute for Microbial Diseases, Osaka University, Suita 565-0871, Japan.
authors: Tatsuo
authors: T
authors: Shioda
authors: Tsukuba Primate Research Center, National Institute of Biomedical Innovation, Tsukuba 305-0843, Japan.|Primate Research Institute, Kyoto University, Inuyama 484-8506, Japan.
authors: Hirofumi
authors: H
authors: Akari
authors: Department of Viral Infections, Research Institute for Microbial Diseases, Osaka University, Suita 565-0871, Japan.
authors: Emi E
authors: EE
authors: Nakayama
mesh_terms: D000818:Animals; D021984:Cyclophilin A / Q000235:genetics*; D014644:Genetic Variation; D015497:HIV-1 / Q000276:immunology; D015498:HIV-2 / Q000276:immunology; D006239:Haplotypes; D007214:Indonesia; D008252:Macaca fascicularis / Q000276:immunology*; D008296:Malaysia; D008969:Molecular Sequence Data; D010679:Philippines; D058974:Phylogeography; D020033:Protein Isoforms / Q000235:genetics; D017422:Sequence Analysis, DNA
chemical_list: D020033:Protein Isoforms; D021984:Cyclophilin A