4.4 Article

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

Journal

VIROLOGY
Volume 354, Issue 1, Pages 15-27

Publisher

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.virol.2006.06.031

Keywords

TRIM5 alpha; single nucleotide polymorphism; HIV-1; HIV infections; disease susceptibility; genetics; haplotype

Categories

Funding

  1. Intramural NIH HHS Funding Source: Medline
  2. NCI NIH HHS [N01-CO-12400] Funding Source: Medline
  3. NHLBI NIH HHS [HL54785] Funding Source: Medline
  4. NIAID NIH HHS [AI28691, AI063987] Funding Source: Medline

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TRIM5 alpha 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 TRIM5 alpha 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 TRIM5 alpha 136Q was relatively elevated in uninfected individuals, suggesting a possible protective effect. TRIM5 alpha 136Q protein exhibited slightly better anti-HIV-1 activity in tissue culture than the TRIM5 alpha R136 protein. The 43Y variant of TRIM5 alpha 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. (c) 2006 Elsevier Inc. All rights reserved.

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