The lack of appropriate animal models that utilizes HIV-1 as the challenge virus is a major impediment to HIV/AIDS research. A major reason underlying the inability of HIV-1 to replicate in nonhuman primate cells is the existence of host antiviral restriction factors. The intrinsic antiviral proteins in host cells are described as restriction factors. The understanding of restriction factors and their mechanism in different primates would undoubtedly facilitate the development of HIV/AIDS animal models. TRIM5α is an important restriction factor and can restrict the infection of several retroviruses including HIV-1 in a species-specific fashion. TRIM5-cyclophilin A (TRIMCyp) gene is an unusual TRIM5 locus found in New World and Old World monkeys. The different TRIMCyp genotypes of four primates (110 samples) including assam macaque (Macaca assamensis), tibetan macaque (Macaca thibetana), stump-tailed macaque (Macaca arctoides) and Chinese rhesus macaques (Macaca mulatta) were studied in this paper. We firstly found that TRIM5-CypA fusion gene exist in Macaca assamensis. The TRIMCyp of Macaca assamensis also results from the retrotransposition of CypA pseudogene cDNA into 3'-UTR of TRIM5 gene like TRIMCyp of Macaca leonina. Moreover, there is an extremely high sequence homology between TRIMCyp genes from Macaca assamensis and Macaca leonina. Besides, we also found the G-to-T mutation (G/T) in the 3'-splicing site of TRIM5 intron 6, which was identical to Macaca leonina. Furthermore, We identified four different alternative splicing isoforms of TRIMCyp gene from Macaca assamensis through RT-PCR and sequencing assays and named them as asmTRIMCypV1-V4 respectively. The asmTRIMCypV2 as the major isoform may involved in the function of the fusion gene product. More work indicated that both exons 7 and 8 were spliced out in the major splicing isoforms during the transciption of the fusion gene. The G-to-T mutation in the 3’-splicing site of TRIM5 intron 6 should prevent the inclusion of exon 7 during splicing. Finally, we performed the alignment of putative CypA animo acid sequences of species variants of primates TRIMCyps and found that both TRIMCyps form Macaca assamensis and Macaca fascicularis with the same amino acid mutation sites related to the restriction of different retroviruses in their CypA domain, which suggested that TRIMCyps form Macaca assamensis and Macaca fascicularis may have the similar restriction activity for protecting the host from various retroviruses infection.
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