期刊
AIDS
卷 23, 期 16, 页码 2091-2100出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/QAD.0b013e328331567a
关键词
association; HIV-1; polymorphism; susceptibility; TRIM5
资金
- Ministry of Health, Labor and Welfare, Japan
- Japan Health Science Foundation
- Founding Research Centers for Emerging and Reemerging Infection Disease
- Research on Publicly Essential Drugs and Medical Devices
- Ministry of Education, Culture, Sports, Science, and Technology (MEXT), Japan
- Heiwa Nakajima Foundation
- Japan Society for the Promotion of Science
- Department of Biotechnology (DBT)
- Ministry of Science and Technology
- Government of India and the Indian Council of Medical Research (ICMR)
Objective: TRIM5 alpha is one of the factors contributing to intracellular defense mechanisms against HIV-1 infection. We investigated the association of TRIM5 alpha sequence variations with the susceptibility to HIV-1 infection in Japanese and Indian. Design: Sequence variations in TRIM5 alpha were investigated in HIV-1-infected patients and ethnic-matched controls. Functional alterations caused by rare variants were analyzed. Methods: We sequenced TRIM5 alpha-exon 2 in both Japanese (94 HIV-1-infected patients and 487 controls) and Indian (101 HIV-1-infected patients and 99 controls). Frequency of variants and haplotypes were compared between the HIV-1-infected patients and controls. Functional analyses were performed for two rare variants, Gly110Arg and G176del. Results: The frequency of 43Tyr-allele in the Indian HIV-1-infected patients was significantly lower than that in the ethnic-matched controls (odds ratio=0.52, 95% confidence interval = 0.31-0.89, P=0.015). A similar tendency was observed in Japanese sample, although it was not statistically significant (odds ratio = 0.67, 95% confidence interval = 0.43-1.05, P=0.095). On the other hand, haplotype analyses revealed that the haplotype carrying the 43Tyr-allele was significantly associated with the reduced susceptibility to HIV-1 infection in both ethnic groups. Functional analysis revealed that Gly110Arg variant weakened the anti-HIV-1 and anti-HIV-2 activities of human TRIM5a, whereas the truncated G176del-TRIM5 enhanced the antiviral activity of coexpressed TRIM5a. Epidemiological data were consistent in that Gly110Arg and G176del were associated with the susceptibility to and protection from HIV-1 infection, respectively. Conclusion: Both common and rare variants of TRIM5a are associated with the susceptibility to HIV-1 infection. (C) 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
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