Effects of human TRIM5α polymorphisms on antiretroviral function and susceptibility to human immunodeficiency virus infection

Hassan Javanbakht, Ping An, Bert Gold, Desiree C. Petersen, Colm O'Huigin, George W. Nelson, Stephen J. O'Brien, Gregory D. Kirk, Roger Detels, Susan Buchbinder, Sharyne Donfield, Sergey Shulenin, Byeongwoon Song, Michel J. Perron, Matthew Stremlau, Joseph Sodroski, Michael Dean, Cheryl Winkler

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)15-27
Number of pages13
JournalVirology
Volume354
Issue number1
DOIs
StatePublished - Oct 10 2006

Keywords

  • Disease susceptibility
  • Genetics
  • HIV infections
  • HIV-1
  • Haplotype
  • Single nucleotide polymorphism
  • TRIM5α

ASJC Scopus subject areas

  • Virology

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  • Cite this

    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. (2006). Effects of human TRIM5α polymorphisms on antiretroviral function and susceptibility to human immunodeficiency virus infection. Virology, 354(1), 15-27. https://doi.org/10.1016/j.virol.2006.06.031