A novel fusion gene, TRIM5-Cyclophilin A in the pig-tailed macaque determines its susceptibility to HIV-1 infection.
OBJECTIVE
In Old World monkeys, the tripartite motif 5alpha (TRIM5alpha) protein confers resistance to HIV-1 infection following virus entry into host cells. However, the pig-tailed macaque (Macaca nemestrina) is an exception and is susceptible to HIV-1 infection. This study dissects the molecular mechanism of the pig-tailed macaque's susceptibility to HIV-1 infection.


METHODS
Genomic sequencing and expression analysis of the TRIM5alpha gene was conducted in the pig-tailed macaque. A novel TRIM5-Cyclophilin A fusion gene isoform was identified and subsequently cloned into the pcDNA3.1(+) expression vector. This construct was transfected into HeLa-T4 or HeLa cells which were then infected with the HIV-1IIIB or HIV-GFP-VSVG pseudotyped virus, to examine the effects of the TRIM5-Cyclophilin A fusion protein on HIV-1 infection.


RESULTS
A novel TRIM5-Cyclophilin A fusion gene (mnTRIMCyp) in the pig-tailed macaque was found and its fusion pattern is different from the known fusion gene in the owl monkey (owlTRIMCyp). TRIMCyp protein expression in transfected cells was confirmed by western blotting. The tests using HIV-1IIIB and HIV-GFP-VSVG pseudotyped virus indicated that mnTRIMCyp did not inhibit HIV-1 replication at various multiplicities of infection.


CONCLUSIONS
The mnTRIMCyp fusion protein does not restrict replication of HIV-1, which provides a potential molecular mechanism that might explain why the pig-tailed macaque is prone to HIV-1 infection, the only known exception in Old World monkeys.
Liao
Cheng-Hong
CH
Kunming Primate Research Center, Chinese Academy of Sciences, Kunming, Yunnan, China.
Kuang
Yi-Qun
YQ
Liu
Hong-Liang
HL
Zheng
Yong-Tang
YT
Su
Bing
B
D000595:Amino Acid Sequence; D000818:Animals; D016645:Aotidae / Q000235:genetics; D001483:Base Sequence; D004198:Disease Susceptibility; D015658:HIV Infections / Q000235:genetics / Q000662:veterinary*; D015497:HIV-1 / Q000502:physiology*; D006367:HeLa Cells / Q000821:virology; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D008254:Macaca nemestrina / Q000235:genetics* / Q000821:virology; D008969:Molecular Sequence Data; D008992:Monkey Diseases / Q000235:genetics*; D016254:Mutagenesis, Insertional; D050506:Mutant Chimeric Proteins / Q000235:genetics* / Q000502:physiology; D018626:Retroelements; D013045:Species Specificity; D053586:Virus Internalization; D014779:Virus Replication
D050506:Mutant Chimeric Proteins; D018626:Retroelements; C526560:TRIM5-cyclophilin A protein, Macaca nemestrina