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.
aPublic Health Agency of Canada, National Microbiology Laboratory, Winnipeg, Manitoba, Canada
bDepartment of Medical Microbiology, University of Nairobi, Nairobi, Kenya
cDepartment of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada.
Received 6 January, 2010
Revised 13 April, 2010
Accepted 23 April, 2010
Correspondance to Dr Ma Luo, 1015 Arlington Street, Winnipeg, MB R3E 3R2, Canada. Tel: +1 204 789 5072; fax: +1 204 784 4835; e-mail: Ma_Luo@phac-aspc.gc.ca