Title

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

Authors

Hassan Javanbakht, Harvard Medical School
Ping An, National Cancer Institute at Frederick
Bert Gold, National Cancer Institute at Frederick
Desiree C. Petersen, Tygerberg Medical School - South Africa
Colm O'Huigin, National Cancer Institute at Frederick
George W. Nelson, National Cancer Institute at Frederick
Roger Detels, University of California - Los Angeles
Susan Buchbinder, University of California - San Francisco
Sharyne Donfield, Rho, Inc.
Sergey Shulenin, National Cancer Institute at Frederick
Byeongwoon Song, Harvard Medical School
Michel J. Perron, Harvard Medical School
Matthew Stremlau, Harvard Medical School
Joseph Sodroski, Harvard Medical School
Michael Dean, National Cancer Institute at Frederick
Cheryl Winkler, National Cancer Institute at Frederick

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

NSUWorks Citation

Javanbakht, Hassan; Ping An; Bert Gold; Desiree C. Petersen; Colm O'Huigin; George W. Nelson; Roger Detels; Susan Buchbinder; Sharyne Donfield; Sergey Shulenin; Byeongwoon Song; Michel J. Perron; Matthew Stremlau; Joseph Sodroski; Michael Dean; and Cheryl Winkler. 2006. "Effects of Human TRIM5α Polymorphisms on Antiretroviral Function and Susceptibility to Human Immunodeficiency Virus Infection." Virology 354, (1): 15-27. https://nsuworks.nova.edu/cnso_bio_facarticles/515

ORCID ID

0000-0001-7353-8301

ResearcherID

N-1726-2015