Abstract
BackgroundThe 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.ResultsThe 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.ConclusionThe 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.
Highlights
The pig-tailed macaques are the only Old World monkeys known to be susceptible to human immunodeficiency virus type 1 (HIV-1) infection
The New World primate owl monkey (Aotus) expresses a TRIM5-cyclophilin A (CypA) (TRIMCyp) fusion protein, in which the B30.2/SPRY domain of tripartite motif protein 5α (TRIM5α) is replaced by CypA resulting from retrotransposition of the CypA pseudogene cDNA into the seventh intron at the TRIM5 locus
Characterization of the TRIM5-Cyclophilin A (TRIMCyp) fusion gene in M. leonina To investigate the correlation between the TRIM5α sequence and the susceptibility to infection by HIV-1 in M. leonina, the genomic sequence of the TRIM5 locus of 11 animals from several different populations was analyzed (Table 1)
Summary
The pig-tailed macaques are the only Old World monkeys known to be susceptible to human immunodeficiency virus type 1 (HIV-1) infection. The host restriction factor tripartite motif protein 5α (TRIM5α) potently blocks HIV-1 replication in rhesus macaque (M. mulatta) through species-specific post-entry restriction in Old World monkeys [5]. The New World primate owl monkey (Aotus) expresses a TRIM5-CypA (TRIMCyp) fusion protein, in which the B30.2/SPRY domain of TRIM5α is replaced by CypA resulting from retrotransposition of the CypA pseudogene cDNA into the seventh intron at the TRIM5 locus. We and others reported that in pigtailed macaques the B30.2/SPRY domain is replaced by retrotransposed CypA in the 3'-UTR of TRIM5 in a fashion different from that in the owl monkey, resulting in the failure of restriction to HIV-1 replication in pig-tailed macaques [13,14,15,16,17]
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