Effects of Human Trim5alpha Polymorphisms on Antiretroviral Function and Susceptibility to Human Immunodeficiency Virus Infection.
From: Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Division of AIDS, Harvard Medical School, Boston, MA 02115, USA.
Virology
- Publish Date: Oct 2006
- ISSN: 0042-6822
- Volume: 354
- Issue: 1
- Pages: 15-27
- Medium: Print
- Language: English
- Citation (JAMA): Javanbakht Hassan, An Ping, Gold Bert, et al. Effects of Human Trim5alpha Polymorphisms on Antiretroviral Function and Susceptibility to Human Immunodeficiency Virus Infection.. Virology Oct 2006;354:15-27
Abstract
TRIM5alpha 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 TRIM5alpha 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 TRIM5alpha 136Q was relatively elevated in uninfected individuals, suggesting a possible protective effect. TRIM5alpha 136Q protein exhibited slightly better anti-HIV-1 activity in tissue culture than the TRIM5alpha R136 protein. The 43Y variant of TRIM5alpha 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.
Mesh Headings (Keywords): Adolescent, Adult, African Americans, Amino Acid Substitution, Animals, Carrier Proteins, Cell Line, Child, Child, Preschool, Disease Susceptibility, Dogs, Exons, Gene Frequency, Green Fluorescent Proteins, HIV Infections, HIV-1, Haplotypes, Humans, Infant, Infant, Newborn, Introns, Leukemia Virus, Murine, Logistic Models, Polymorphism, Single Nucleotide
Check for Full Text / PubMed Unique Identifier (PMID): 16887163
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