An HIV-1 Resistance Polymorphism in TRIM5 alpha Gene Among Chinese Intravenous Drug Users

Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, China.
JAIDS Journal of Acquired Immune Deficiency Syndromes (Impact Factor: 4.56). 11/2010; 56(4):306-11. DOI: 10.1097/QAI.0b013e318205a59b
Source: PubMed


TRIM5α has species-specific restriction activity against replication of many retroviruses, including HIV-1. Though human also express TRIM5α protein, it is less potent in suppressing infection of HIV-1 than most orthologs of other nonhuman primates. Previous association studies suggested that polymorphisms in TRIM5α gene might protect against HIV-1 infection. However, the exact variation accounting for this protective effect was not certain.
One thousand two hundred ninety-four Chinese intravenous drug users (IDUs), including 1011 Hans and 283 Dai subjects, were investigated for sequence variations in TRIM5α and association with HIV-1 resistance. Resequencing of the putative functional domains in exon2 and exon8 was carried out in 1151 subjects, along with exon2 resequencing in a further 143 HIV-1-infected IDUs.
We identified 14 different nucleotide variants, including 4 with minor allele frequency >0.05. We observed that the frequency of 43Y homozygote in seronegative IDUs was significantly higher than that in the HIV-1-infected IDUs, suggesting a protective effect among the homozygote subjects [odds ratio (95% confidence interval) = 0.46 (0.22 to 0.94), P = 0.033, Mantel-Haenszel test].
we concluded that H43Y might account for the HIV-1 resistance due to TRIM5α gene in Chinese IDUs.

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Available from: Feng-Liang Liu, Dec 15, 2015
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    • "Interestingly, we also found that the 43Y-allele was found less frequently in Japanese and Indian HIV-1-infected subjects than in ethnicity-matched controls (Nakajima et al., 2009). Furthermore, Liu et al. (2011) reported that the frequency of H43Y homozygotes was higher in seronegative intravenous drug users than in HIV-infected drug users. The reasons for the discrepancy between the epidemiological and functional effects of H43Y remain unclear, and further studies are required to clarify the impact of H43Y on susceptibility to HIV-1 transmission and/or rate of progression to AIDS. "
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