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Effects of human TRIM5 alpha polymorphisms on antiretroviral function and susceptibility to human immunodeficiency virus infection

  1. Author:
    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.

  2. Author Address

    NCI, Mol Genet Epidemiol Sec, Frederick, MD 21702 USA. NCI, SAIC Frederick, Basic Res Program, Lab Genom Divers, Frederick, MD 21702 USA. Harvard Univ, Sch Med, Div AIDS, Dept Canc Immunol & AIDS,Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Stellenbosch, Tygerberg Med Sch, Dept Med Virol, ZA-7505 Tygerberg, South Africa. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. Univ Calif Los Angeles, Sch Publ Hlth, Dept Epidemiol, Ctr Hlth Sci, Los Angeles, CA 90095 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Rho Inc, Chapel Hill, NC 27514 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA.;Winkler, C, NCI, Mol Genet Epidemiol Sec, Bldg 560,Room 21-19, Frederick, MD 21702 USA.;winkler@ncifcrf.gov
    1. Year: 2006
    2. Date: Oct
  2. Journal: Virology
    1. 354
    2. 1
    3. Pages: 15-27
  4. Type of Article: Article
  5. ISSN: 0042-6822
  1. Abstract:

    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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External Sources

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  2. DOI: 10.1016/j.virol.2006.06.031
  3. View record in Web of Science®
  4. WOS: 000241178500003

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