Effects of Human TRIM5α Polymorphisms on Antiretroviral Function and Susceptibility to Human Immunodeficiency Virus Infection
TRIM5α, Single nucleotide polymorphism, HIV-1, HIV infections, Disease susceptibility, Genetics, Haplotype
TRIM5α 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 TRIM5α 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 TRIM5α 136Q was relatively elevated in uninfected individuals, suggesting a possible protective effect. TRIM5α 136Q protein exhibited slightly better anti-HIV-1 activity in tissue culture than the TRIM5α R136 protein. The 43Y variant of TRIM5α 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.
Javanbakht, Hassan; Ping An; Bert Gold; Desiree C. Petersen; Colm O'Huigin; George W. Nelson; Roger Detels; Susan Buchbinder; Sharyne Donfield; Sergey Shulenin; Byeongwoon Song; Michel J. Perron; Matthew Stremlau; Joseph Sodroski; Michael Dean; and Cheryl Winkler. 2006. "Effects of Human TRIM5α Polymorphisms on Antiretroviral Function and Susceptibility to Human Immunodeficiency Virus Infection." Virology 354, (1): 15-27. http://nsuworks.nova.edu/cnso_bio_facarticles/515