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Effects of human TRIM5α polymorphisms on antiretroviral function and susceptibility to human immunodeficiency virus infection
- Source :
-
Virology . Oct2006, Vol. 354 Issue 1, p15-27. 13p. - Publication Year :
- 2006
-
Abstract
- 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. [Copyright &y& Elsevier]
- Subjects :
- *HIV infections
*HIV
*GENETIC polymorphisms
*VIRUS diseases
*TISSUE culture
Subjects
Details
- Language :
- English
- ISSN :
- 00426822
- Volume :
- 354
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- Virology
- Publication Type :
- Academic Journal
- Accession number :
- 22609648
- Full Text :
- https://doi.org/10.1016/j.virol.2006.06.031