Biology Faculty Articles

Title

Effects of Human TRIM5α Polymorphisms on Antiretroviral Function and Susceptibility to Human Immunodeficiency Virus Infection

Document Type

Article

Publication Date

10-10-2006

Publication Title

Virology

Keywords

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

ISSN

0042-6822

Volume

354

Issue/No.

1

First Page

15

Last Page

27

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.

Comments

© 2006 Elsevier Inc. All rights reserved.

Additional Comments

National Institutes of Health grant #s: AI063987, HL54785, AI28691; National Cancer Institute contract #: NO1-CO-12400

ORCID ID

0000-0001-7353-8301

ResearcherID

N-1726-2015

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