Javanbakht, H., An, P., Gold, B., Petersen, D. C., O'Huigin, C., Nelson, G. W., O'Brien, S. J., Kirk, G. D., Detels, R., Buchbinder, S., Donfield, S., Shulenin, S., Song, B., Perron, M. J., Stremlau, M., Sodroski, J., Dean, M., Winkler, C.
Effects of Human TRIM5alpha Polymorphisms on Antiretroviral Function and Susceptibility to Human Immunodeficiency Virus Infection
Virology. 2006 Oct 10; 354(1): 15-27.
TRIM5alpha acts on several retroviruses, including human immunodeficiency virus (HIV-1), to restrict cross-species transmission. Using natural history cohorts and tissue culture systems, we examined the effect of polymorphism in human TRIM5alpha on HIV-1 infection. In African Americans, the frequencies of two non-coding SNP variant alleles in exon 1 and intron 1 of TRIM5 were elevated in HIV-1-infected persons compared with uninfected subjects. By contrast, the frequency of the variant allele encoding TRIM5alpha 136Q was relatively elevated in uninfected individuals, suggesting a possible protective effect. TRIM5alpha 136Q protein exhibited slightly better anti-HIV-1 activity in tissue culture than the TRIM5alpha R136 protein. The 43Y variant of TRIM5alpha was less efficient than the H43 variant at restricting HIV-1 and murine leukemia virus infections in cultured cells. The ancestral TRIM5 haplotype specifying no observed variant alleles appeared to be protective against infection, and the corresponding wild-type protein partially restricted HIV-1 replication in vitro. A single logistic regression model with a permutation test indicated the global corrected P value of <0.05 for both SNPs and haplotypes. Thus, polymorphism in human TRIM5 may influence susceptibility to HIV-1 infection, a possibility that merits additional evaluation in independent cohorts.
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