Impact of novel TRIM5α variants, Gly110Arg and G176del, on the anti-HIV-1 activity and the susceptibility to HIV-1 infection
TRIM5α is one of the factors contributing to intracellular defense mechanisms against HIV-1 infection. We investigated the association of TRIM5α sequence variations with the susceptibility to HIV-1 infection in Japanese and Indian.Design:
Sequence variations in TRIM5α were investigated in HIV-1-infected patients and ethnic-matched controls. Functional alterations caused by rare variants were analyzed.Methods:
We sequenced TRIM5α-exon 2 in both Japanese (94 HIV-1-infected patients and 487 controls) and Indian (101 HIV-1-infected patients and 99 controls). Frequency of variants and haplotypes were compared between the HIV-1-infected patients and controls. Functional analyses were performed for two rare variants, Gly110Arg and G176del.Results:
The frequency of 43Tyr-allele in the Indian HIV-1-infected patients was significantly lower than that in the ethnic-matched controls (odds ratio = 0.52, 95% confidence interval = 0.31–0.89, P = 0.015). A similar tendency was observed in Japanese sample, although it was not statistically significant (odds ratio = 0.67, 95% confidence interval = 0.43–1.05, P = 0.095). On the other hand, haplotype analyses revealed that the haplotype carrying the 43Tyr-allele was significantly associated with the reduced susceptibility to HIV-1 infection in both ethnic groups. Functional analysis revealed that Gly110Arg variant weakened the anti-HIV-1 and anti-HIV-2 activities of human TRIM5α, whereas the truncated G176del-TRIM5 enhanced the antiviral activity of coexpressed TRIM5α. Epidemiological data were consistent in that Gly110Arg and G176del were associated with the susceptibility to and protection from HIV-1 infection, respectively.Conclusion:
Both common and rare variants of TRIM5α are associated with the susceptibility to HIV-1 infection.