A Trim5alpha Exon 2 Polymorphism is Associated with Protection from HIV-1 Infection in Pumwani Sexworker Cohort

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, while huTRIM5α lacks this specificity. Previous studies have suggested that certain polymorphisms in huTRIM5 may enhance or impair the proteins affinity for HIV-1. This study investigates the role of TRIM5 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 Trim5alpha gene, including exon 2, from 1032 women enrolled in the Pumwani sex worker cohort was amplified and sequenced. SNPs and haplotypes were compared between HIV-1 positive and resistant women.

Methods

The TRIM5 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 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; OR:2.991; CI95%: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.

Keywords: TRIM5α, Single nucleotide polymorphism, HIV-1, Sex Workers, Taxonomy-based Sequence Analysis, Disease Association, Disease Resistance