Genotyping of TRIM5 locus in northern pig-tailed macaques (Macaca leonina), a primate species susceptible to Human Immunodeficiency Virus type 1 infection.
BACKGROUND
The pig-tailed macaques are the only Old World monkeys known to be susceptible to human immunodeficiency virus type 1 (HIV-1) infection. We have previously reported that the TRIM5-Cyclophilin A (TRIMCyp) fusion in pig-tailed macaques (Macaca nemestrina) is dysfunctional in restricting HIV-1, which may explain why pig-tailed macaques are susceptible to HIV-1 infection. Similar results have also been reported by other groups. However, according to the current primate taxonomy, the previously reported M. nemestrina are further classified into three species, which all belong to the Macaca spp. This calls for the need to look into the previous studies in more details.


RESULTS
The local species Northern pig-tailed macaque (M. leonina) was analyzed for the correlation of TRIM5 structure and HIV-1 infection. Eleven M. leonina animals were analyzed, and all of them were found to possess TRIM5-CypA fusion at the TRIM5 locus. The transcripts encoding the dysfunctional TRIM5-CypA should result from the G-to-T mutation in the 3'-splicing site of intron 6. Polymorphism in the putative TRIMCyp recognition domain was observed. The peripheral blood mononuclear cells (PBMCs) of M. leonina were susceptible to HIV-1 infection. Consistent with the previous results, expression of the M. leonina TRIMCyp in HeLa-T4 cells rendered the cells resistant to HIV-2ROD but not to SIVmac239 infection.


CONCLUSIONS
The susceptibility of M. leonina to HIV-1 infection is due to the dysfunctional TRIM5-CypA fusion in the TRIM5 locus. This finding should broaden our perspective in developing better HIV/AIDS non-human primate animal models.
Kuang
Yi-Qun
YQ
Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, PR China. kuangyq03@post.kiz.ac.cn
Tang
Xia
X
Liu
Feng-Liang
FL
Jiang
Xue-Long
XL
Zhang
Ya-Ping
YP
Gao
Guangxia
G
Zheng
Yong-Tang
YT
D000818:Animals; D001483:Base Sequence; D004247:DNA / Q000032:analysis / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005838:Genotype; D015658:HIV Infections / Q000235:genetics / Q000378:metabolism / Q000662:veterinary* / Q000821:virology; D015497:HIV-1; D006367:HeLa Cells; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology; D008251:Macaca; D008969:Molecular Sequence Data; D008992:Monkey Diseases / Q000235:genetics* / Q000378:metabolism / Q000821:virology; D050506:Mutant Chimeric Proteins / Q000096:biosynthesis / Q000235:genetics*; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide; D013045:Species Specificity
D050506:Mutant Chimeric Proteins; C526560:TRIM5-cyclophilin A protein, Macaca nemestrina; D004247:DNA