@article{240321ae58bb45b0b3eff7f4d2999e80,
title = "Effects of human TRIM5α polymorphisms on antiretroviral function and susceptibility to human immunodeficiency virus infection",
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.",
keywords = "Disease susceptibility, Genetics, HIV infections, HIV-1, Haplotype, Single nucleotide polymorphism, TRIM5α",
author = "Hassan Javanbakht and Ping An and Bert Gold and Petersen, {Desiree C.} and Colm O'Huigin and Nelson, {George W.} and O'Brien, {Stephen J.} and Kirk, {Gregory D.} and Roger Detels and Susan Buchbinder and Sharyne Donfield and Sergey Shulenin and Byeongwoon Song and Perron, {Michel J.} and Matthew Stremlau and Joseph Sodroski and Michael Dean and Cheryl Winkler",
note = "Funding Information: We thank Ms. Yvette McLaughlin and Ms. Sheri Farnum for manuscript preparation; Elizabeth Binns-Roemer, Yuchun Zhou and Julie Sawitske for excellent technical assistance; Bailey Kessing for informatics support; and Drs. Michael Smith, Taras Oleksyk and James Lautenberger and the reviewers for their helpful suggestions. We are also grateful to Dr. James Goedert for clinical data and patient DNA samples from the MHCS. This work was supported in part by grants from the National Institutes of Health (AI063987, HL54785 and a Center for AIDS Research Award [AI28691]), the International AIDS Vaccine Initiative, the Bristol-Myers Squibb Foundation and the late William F. McCarty-Cooper. This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research under contract #NO1-CO-12400. This study was also supported by the South African AIDS Vaccine Initiative (SAAVI), the Poliomyelitis Research Foundation and the Medical Research Council (MRC) of South Africa.The content of this publication does not necessarily reflect the views of the Department of Health and Human Services nor does mention of trade names, commercial products or organizations imply endorsement by the U.S. Government. ",
year = "2006",
month = oct,
day = "10",
doi = "10.1016/j.virol.2006.06.031",
language = "English (US)",
volume = "354",
pages = "15--27",
journal = "Virology",
issn = "0042-6822",
publisher = "Academic Press Inc.",
number = "1",
}