An HIV-1 Resistance Polymorphism in TRIM5α Gene Among Chinese Intravenous Drug Users

Background: TRIM5 alpha has species-specific restriction activity against replication of many retroviruses, including HIV-1. Though human also express TRIM5 alpha 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 TRIM5 alpha gene might protect against HIV-1 infection. However, the exact variation accounting for this protective effect was not certain. Methods: One thousand two hundred ninety-four Chinese intravenous drug users (IDUs), including 1011 Hans and 283 Dai subjects, were investigated for sequence variations in TRIM5 alpha 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. Results: 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]. Conclusions: we concluded that H43Y might account for the HIV-1 resistance due to TRIM5 alpha gene in Chinese IDUs.