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

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Abstract

Objective:

The innate immune component TRIM5α has the ability to restrict retrovirus infection in a species-specific manner. TRIM5α of some primate species restricts infection by HIV-1, whereas human TRIM5α lacks this specificity. Previous studies have suggested that certain polymorphisms in human TRIM5α may enhance or impair the proteins affinity for HIV-1. This study investigates the role of TRIM5α 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 TRIM5α gene, including exon 2, from 1032 women enrolled in the Pumwani sex worker cohort was amplified and sequenced. Single-nucleotide polymorphisms (SNPs) and haplotypes were compared between HIV-1-positive and resistant women.

Methods:

The TRIM5α 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 TRIM5α 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 TRIM5α 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 TRIM5α confers protection against HIV-1 in the Pumwani sex worker cohort.

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