A TRIM5alpha exon 2 polymorphism is associated with protection from HIV-1 infection in the Pumwani sex worker cohort.
OBJECTIVE
The innate immune component TRIM5alpha has the ability to restrict retrovirus infection in a species-specific manner. TRIM5alpha of some primate species restricts infection by HIV-1, whereas human TRIM5alpha lacks this specificity. Previous studies have suggested that certain polymorphisms in human TRIM5alpha may enhance or impair the proteins affinity for HIV-1. This study investigates the role of TRIM5alpha 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.


METHODS
A 1 kb fragment of the TRIM5alpha 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 TRIM5alpha 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 TRIM5alpha 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 TRIM5alpha 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 TRIM5alpha confers protection against HIV-1 in the Pumwani sex worker cohort.
Price
Heather
H
Public Health Agency of Canada, National Microbiology Laboratory, Winnipeg, Manitoba, Canada.
Lacap
Philip
P
Tuff
Jeff
J
Wachihi
Charles
C
Kimani
Joshua
J
Ball
Terry B
TB
Luo
Ma
M
Plummer
Francis A
FA
D000328:Adult; D000090103:Antiviral Restriction Factors; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology*; D015331:Cohort Studies; D005091:Exons / Q000502:physiology; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000235:genetics / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006239:Haplotypes / Q000502:physiology; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D007630:Kenya; D020641:Polymorphism, Single Nucleotide / Q000235:genetics / Q000276:immunology*; D011477:Sex Work; D012725:Sexual Behavior; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases
D000090103:Antiviral Restriction Factors; D002352:Carrier Proteins; D000070584:Tripartite Motif Proteins; C477346:TRIM5 protein, human; D044767:Ubiquitin-Protein Ligases