Association between TLR3 rs3775291 and resistance to HIV among highly exposed Caucasian intravenous drug users

Kristi Huik, Radko Avi, Merit Pauskar, Eveli Kallas, Ene Ly Jõgeda, Tõnis Karki, Kristina Marsh, Don Des Jarlais, Anneli Uusküla, Irja Lutsar

Research output: Contribution to journalArticle

Abstract

Background: TLR3 recognizes dsRNA and triggers immune responses against RNA and DNA viruses. A polymorphism in TLR3, rs3775291 (Leu412Phe), has been associated with the increased susceptibility to enteroviral myocarditis, protection against tick-borne encephalitis virus and HIV-1 infection. We investigated Caucasian intravenous drug users (IDUs) and blood donors in order to evaluate the associations between TLR3 genotypes and susceptibility to HIV infection. Materials and methods: A total of 345 Caucasian IDUs were recruited, 50% of them were HIV positive, 89% HCV and 77% HBV positive. Based on their history of needle sharing, 20 of the HIV negative IDUs were classified as highly exposed HIV seronegatives (HESNs), 68 as non-HESNs and 85 as unexposed. The control group consisting of 497 blood donors tested negative for all three viruses. TLR3 rs3775291 were determined by using TaqMan Allelic Discrimination Assay. Results: The TLR3 rs3775291 T allele frequency was similar among the HIV negative and HIV positive IDUs and blood donors - 36%, 31% and 34%, respectively. The frequency of persons possessing at least one TLR3 rs3775291 T allele was significantly higher in HESNs compared with blood donors and HIV positive IDUs (80% vs. 55%; p=0.037 and 80% vs. 53%; p=0.031, respectively). In the univariate analysis, persons who possessed at least one T allele had reduced odds of being HIV seropositive (OR=0.29, 95% CI=0.09-0.90). This association remained significant (OR=0.25, 95% CI=0.07-0.87) after the adjustment for other co-variates (HCV, HBV serostatus and duration of intravenous drug use). Conclusions: The TLR3 rs3775291 T allele has a protective effect against HIV infection among HESNs IDUs.

Original languageEnglish (US)
Pages (from-to)78-82
Number of pages5
JournalInfection, Genetics and Evolution
Volume20
DOIs
StatePublished - Dec 2013

Keywords

  • Highly exposed HIV seronegatives
  • Intravenous drug users
  • Leu412Phe
  • TLR3

ASJC Scopus subject areas

  • Microbiology
  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics
  • Microbiology (medical)
  • Infectious Diseases

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