Polymorphisms in Toll-like receptor 3 confer natural resistance to human herpes simplex virus type 2 infection.
ABSTRACT Lack of Toll-like receptor 3 (TLR3) functional activity predisposes children to human herpesvirus 1 (HSV-1) encephalitis. In this study, we have investigated whether there is any link between TLR3 and adult HSV-2 infection by studying genetic variations in TLR3. The frequency of four single-nucleotide polymorphisms (SNPs) in the TLR3 gene in 239 patients with genital HSV-2 infection and 162 healthy controls, as well as the impact of these variants on TLR3 gene-expression levels, were compared. Two SNPs in the TLR3 gene (rs13126816 and rs3775291) were associated with a reduced incidence of HSV-2 infection. The minor allelic variants at both rs13126816 and rs3775291 were more common among healthy HSV-2-seronegative subjects than among HSV-2-infected individuals. This was even more apparent in HSV-1-seronegative individuals. There was, however, no association between any of the four TLR3 SNPs and HSV-2 disease severity, as they were expressed at similar proportions in asymptomatic and symptomatic HSV-2-infected patients alike. Furthermore, when assessing TLR3 mRNA expression in a limited number of HSV-2-infected individuals, we found that individuals carrying the homozygous genotypes for the minor alleles had significantly higher levels of TLR3 mRNA expression in peripheral blood mononuclear cells in response to HSV-2 stimulation than individuals that were homozygous for the major allele variants. Taken together, these results suggest that genetic variations in TLR3 may affect the susceptibility to HSV-2 infection in humans.
SourceAvailable from: Francisco Lozano[Show abstract] [Hide abstract]
ABSTRACT: Infection is the leading cause of complication after liver transplantation, causing morbidity and mortality in the first months after surgery. Allograft rejection is mediated through adaptive immunological responses, and thus immunosuppressive therapy is necessary after transplantation. In this setting, the presence of genetic variants of innate immunity receptors may increase the risk of post-transplant infection, in comparison with patients carrying wild-type alleles. Numerous studies have investigated the role of genetic variants of innate immune receptors and the risk of complication after liver transplantation, but their results are discordant. Toll-like receptors and mannose-binding lectin are arguably the most important studied molecules; however, many other receptors could increase the risk of infection after transplantation. In this article, we review the published studies analyzing the impact of genetic variants in the innate immune system on the development of infectious complications after liver transplantation.World Journal of Gastroenterology 08/2014; 20(32):11116-11130. DOI:10.3748/wjg.v20.i32.11116 · 2.43 Impact Factor
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ABSTRACT: Toll-like receptor-3 (TLR3) is a cellular receptor that may recognize double-stranded RNA (dsRNA) from viruses, resulting in production of proinflammatory cytokines and interferons, which are important for the adaptive immune response. To analyze the association between Toll-like receptor-3 (TLR3) polymorphisms (rs3775291 and rs13126816) and virologic response to pegylated interferon-alpha plus ribavirin (pegIFNα/RBV) therapy in HIV/HCV coinfected patients. We performed a retrospective study in 321 naïve patients treated with pegIFNα/RBV. Genotyping was performed by using the GoldenGate(®) assay with VeraCode(®). The outcome variables were early virologic response (EVR) and sustained virologic response (SVR). In a multivariate analysis, rs3775291 A allele decreased the likelihood of achieving EVR (aOR=0.20; p=0.018) and SVR (aOR=0.38; p=0.024). Regarding rs13126816, the percentage of EVR decreased with each minor A allele (p=0.034) in HCV-GT2/3 patients, although no significant association was obtained in the multivariate analysis (p=0.076). Regarding TLR3 haplotypes (comprised of rs3775291 and rs13126816), GT2/3 patients with AA haplotype had decreased odds of achieving EVR (p=0.030), whereas GG haplotype increased the likelihood (p=0.018). Regarding SVR, GG haplotype carriers had increased odds of achieving SVR (p=0.019, p=0.043 and p=0.070 for all, GT2/3 and GT1/4 patients, respectively). Besides, GT1/4 patients with GA haplotype had lower odds of achieving SVR (p=0.039). Our study shows the first evidence that two TLR3 polymorphisms (rs3775291 and rs13126816) seem to be related to the HCV therapy response in HCV/HIV coinfected patients. Copyright © 2015 Elsevier B.V. All rights reserved.Journal of Clinical Virology 02/2015; 65. DOI:10.1016/j.jcv.2015.02.004 · 3.47 Impact Factor
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ABSTRACT: Functional polymorphisms in RNA recognizing toll like receptors (TLR) 3, 7, 8 and toll-interleukin-1 receptor domain containing adapter protein adapter (TIRAP) coding genes were investigated in 120 dengue cases [87 dengue fever (DF) cases and 33 dengue hemorrhagic fever (DHF) cases] and 109 healthy controls to identify their association with clinical outcomes of dengue virus infection. Results revealed significantly lower frequency of TLR3 rs3775291 T allele [DHF vs. DF P = 0.015 odds ratio (OR) with 95% confidence interval (CI) 0.390 (0.160-0.880); DHF vs. HC P = 0.018 OR with 95% CI 0.410 (0.170-0.900)] and ‘T’ allele carriers [DHF vs. DF P = 0.008 OR with 95% CI 0.288 (0.115-0.722); DHF vs. HC P = 0.040 OR with 95% CI 0.393 (0.162-0.956)] and higher frequency of TIRAP rs8177374 ‘C/T’ genotype [DHF vs. HC P = 0.020 OR with 95% CI 2.643 (1.167-5.986)] in DHF. Higher frequency of TLR8 rs3764879-rs3764880 haplotype C-A was observed in male DF cases compared to male HC [P = 0.025 OR with 95% CI 2.185 (1.101-4.336)]. The results suggest that TLR3 and TIRAP gene variants influence the risk for DHF.Immunobiology 10/2014; 220(1). DOI:10.1016/j.imbio.2014.09.020 · 2.81 Impact Factor