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

ABSTRACT: 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.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.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).The TLR3 rs3775291 T allele has a protective effect against HIV infection among HESNs IDUs.

SUBMITTER: Huik K

PROVIDER: S-EPMC4001117 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature

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

Huik Kristi K Avi Radko R Pauskar Merit M Kallas Eveli E Jõgeda Ene-Ly EL Karki Tõnis T Marsh Kristina K Des Jarlais Don D Uusküla Anneli A Lutsar Irja I

Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases 20130817

<h4>Background</h4>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.<h4>Materials and methods</h4>A ...[more]

PMID: 23962581

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Project description:The human immunodeficiency virus 1 (HIV-1) epidemic in China historically stemmed from intravenous drug users (IDUs) in Yunnan. Due to a shared transmission route, hepatitis C virus (HCV)/HIV-1 co-infection is common. Here, we investigated HCV genetic characteristics and baseline drug resistance among HIV-infected IDUs in Yunnan.Blood samples of 432 HIV-1/HCV co-infected IDUs were collected from January to June 2014 in six prefectures of Yunnan Province. Partial E1E2 and NS5B genes were sequenced. Phylogenetic, evolutionary and genotypic drug resistance analyses were performed.Among the 293 specimens successfully genotyped, seven subtypes were identified, including subtypes 3b (37.9%, 111/293), 3a (21.8%, 64/293), 6n (14.0%, 41/293), 1b (10.6%, 31/293), 1a (8.2%, 24/293), 6a (5.1%, 15/293) and 6u (2.4%, 7/293). The distribution of HCV subtypes was mostly related to geographic location. Subtypes 3b, 3a, and 6n were detected in all six prefectures, however, the other four subtypes were detected only in parts of the six prefectures. Phylogeographic analyses indicated that 6n, 1a and 6u originated in the western prefecture (Dehong) and spread eastward and showed genetic relatedness with those detected in Burmese. However, 6a originated in the southeast prefectures (Honghe and Wenshan) bordering Vietnam and was transmitted westward. These subtypes exhibited different evolutionary rates (between 4.35×10-4 and 2.38×10-3 substitutions site-1 year-1) and times of most recent common ancestor (tMRCA, between 1790.3 and 1994.6), suggesting that HCV was multiply introduced into Yunnan. Naturally occurring resistance-associated mutations (C316N, A421V, C445F, I482L, V494A, and V499A) to NS5B polymerase inhibitors were detected in direct-acting antivirals (DAAs)-naïve IDUs.This work reveals the temporal-spatial distribution of HCV subtypes and baseline HCV drug resistance among HIV-infected IDUs in Yunnan. The findings enhance our understanding of the characteristics and evolution of HCV in IDUs and are valuable for developing HCV prevention and management strategies for this population.

Dataset Information

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

Publications

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

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