A TRIM5α exon 2 polymorphism is associated with protection from HIV-1 infection in the Pumwani sex worker cohort

Objective: The innate immune component TRIM5 alpha has the ability to restrict retrovirus infection in a species-specific manner. TRIM5 alpha of some primate species restricts infection by HIV-1, whereas human TRIM5 alpha lacks this specificity. Previous studies have suggested that certain polymorphisms in human TRIM5 alpha may enhance or impair the proteins affinity for HIV-1. This study investigates the role of TRIM5 alpha polymorphisms in resistance/susceptibility to HIV-1 within the Pumwani sex worker cohort in Nairobi, Kenya. A group of women within this cohort remain HIV-1-seronegative and PCR-negative despite repeated exposure to HIV-1 through active sex work. Design: A 1 kb fragment of the TRIM5 alpha gene, including exon 2, from 1032 women enrolled in the Pumwani sex worker cohort was amplified and sequenced. Singlenucleotide polymorphisms (SNPs) and haplotypes were compared between HIV-1-positive and resistant women. Methods: The TRIM5 alpha exon 2 genomic fragment was amplified, sequenced and genotyped. Pypop32-0.6.0 was used to determine SNP and haplotype frequencies and statistical analysis was carried out using SPSS-13.0 for Windows. Results: A TRIM5 alpha SNP (rs10838525) resulting in the amino acid change from arginine to glutamine at codon 136, was enriched in HIV-1-resistant individuals [P = 1.104E-05; odds ratio (OR) 2.991; 95% confidence interval (CI) 1.806 -4.953] and women with 136Q were less likely to seroconvert (P = 0.002; log-rank 12.799). Wild-type TRIM5 alpha exon 2 was associated with susceptibility to HIV-1 (P = 0.006; OR 0.279; 95% CI 0.105-0.740) and rapid seroconversion (P = 0.001; log-rank 14.475). Conclusions: Our findings suggest that a shift from arginine to glutamine at codon 136 in the coiled-coil region of TRIM5 alpha confers protection against HIV-1 in the Pumwani sex worker cohort. (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins