Polymorphisms in RNA sensing toll like receptor genes and its association with clinical outcomes of dengue virus infection

Alagarasu, Kalichamy; Bachal, Rupali; Memane, R. S.; Shah, P.S.; Cecilia, D.

doi:10.1016/j.imbio.2014.09.020

Cited by 22 publications

(16 citation statements)

References 24 publications

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“…DHF women patients with high monocyte and high IgG levels had a greater probability of being TLR8-rs3764880-A/A and rs3764880-A/G, respectively. In the Indian population, a greater frequency of the TLR8 haplotype TLR8-rs3764879-rs3764880 (C-A) was observed in males with DF than in healthy men [19]. In addition, the AA/A genotype has been previously associated with the development of warning signs among dengue infected patients in the Indian population [30].…”

Section: Discussionmentioning

confidence: 96%

“…However, DHF patients with high IgG1 levels were more likely to be TLR3-rs3775291-C/T, and who presented a secondary infection had a lower probability of being TLR3-rs3775291-T/T. In the Indian population, the T allele has been associated with a lower risk of DHF in a dominant mode [19]. It has also been associated with a protective effect against HIV infection among highly exposed HIV seronegative subjects and intravenous drug users [26].…”

Section: Discussionmentioning

confidence: 99%

“…Likewise, the high frequency of the T allele of the SNP TLR3-rs3775291 in adults of India associated with DHF in comparison with DF has been reported. By comparison, the TLR8 C-A haplotype of the SNPs rs3764879 and rs3764880 was found to be associated with DF in adult males from India [19].…”

Section: Introductionmentioning

confidence: 94%

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Association of Genetic Polymorphisms in TLR3, TLR4, TLR7, and TLR8 with the Clinical Forms of Dengue in Patients from Veracruz, Mexico

Posadas-Mondragón

Aguilar-Faisal

Zúñiga

et al. 2020

Viruses

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Dengue manifestations range from a mild form, dengue fever (DF), to more severe forms such as dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). The ability of the host to present one of these clinical forms could be related to polymorphisms located in genes of the Toll-like receptors (TLRs) which activate the pro-inflammatory response. Therefore, the genotyping of single nucleotide genetic polymorphisms (SNPs) in TLR3 (rs3775291 and rs6552950), TLR4 (rs2737190, rs10759932, rs4986790, rs4986791, rs11536865, and rs10983755), TLR7 (rs179008 and rs3853839), and TLR8 (rs3764880, rs5741883, rs4830805, and rs1548731) was carried out in non-genetically related DHF patients, DF patients, and general population (GP) subjects. The SNPs were analyzed by real-time PCR by genotyping assays from Applied Biosystems®. The codominance model showed that dengue patients had a lower probability of presenting the TLR4-rs2737190-G/G genotype (odds ratio (OR) (95% CI) = 0.34 (0.14–0.8), p = 0.038). Dengue patients showed a lower probability of presenting TLR4-rs11536865-G/C genotype (OR (95% CI) = 0.19 (0.05–0.73), p = 0.0092) and had a high probability of presenting the TACG haplotype, but lower probability of presenting the TGCG haplotype in the TLR4 compared to GP individuals (OR (95% CI) = 0.55 (0.35–0.86), p = 0.0084). In conclusion, the TLR4-rs2737190-G/G and TLR4-rs11536865-G/C genotypes and TGCG haplotype were associated with protection from dengue.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

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Association of Genetic Polymorphisms in TLR3, TLR4, TLR7, and TLR8 with the Clinical Forms of Dengue in Patients from Veracruz, Mexico

Posadas-Mondragón

Aguilar-Faisal

Zúñiga

et al. 2020

Viruses

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“…In line with this, it has been described that functional polymorphisms in the human Tlr8 gene may predispose individuals to differential viral susceptibility (14, 69-72). For instance, TLR8C-A haplotypes are associated with dengue fever susceptibility, while TLR8G-G haplotypes are associated with dengue hemorrhagic fever susceptibility (71) and truncated Tlr8 protects against HIV, as rapid decay of Tlr8 mRNA results in induced TNF-α signaling (70). Therefore, TLR8 may function to suppress antiviral immunity through negative regulation of TLR7 signaling.…”

Section: Discussionmentioning

confidence: 99%

TLR8 Couples SOCS-1 and Restrains TLR7-Mediated Antiviral Immunity, Exacerbating West Nile Virus Infection in Mice

Paul

Acharya

et al. 2016

The Journal of Immunology

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West Nile virus (WNV) is a neurotropic, single-stranded RNA (ssRNA) flavivirus that can cause encephalitis, meningitis, and death in humans and mice. Human Toll-like receptor (TLR) 7, 8, and mouse TLR7 recognize viral ssRNA motifs and induce antiviral immunity. However, the role of mouse TLR8 in antiviral immunity is poorly understood. Here, we report that TLR8 deficient (Tlr8−/−) mice were resistant to WNV infection compared to wild-type (WT) controls. Efficient WNV clearance and moderate susceptibility to WNV-mediated neuronal death in Tlr8−/− mice was attributed to overexpression of Tlr7 and an interferon-stimulated gene Isg-56 expression, while reduced expression of the pro-apoptotic gene coding Bcl2-associated X protein (Bax) was observed. Interestingly, suppressor of cytokine signaling -1 (SOCS-1) directly associated with TLR8, but not with TLR7, indicating a novel role for TLR8 regulation of SOCS-1 function, while selective siRNA knockdown of Socs-1 resulted in induced Isg-56 and Tlr7 expression following WNV infection. Collectively, we report that TLR8 coupling with SOCS-1 inhibits TLR7-mediated antiviral immunity during WNV infection in mice.

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“…Single nucleotide polymorphisms (SNPs) within TLR genes, can cause impaired response to TLR ligands in some individials and susceptibility to infections is altered in this population [Tapping et al, ]. For example, Alagarasu et al [] investigated TLR3 polymorphisms in dengue cases. They found that lower frequency of TLR3 rs3775291 T allele in dengue hemorrhagic fever; and they suggested that the T allele of TLR3 rs3775291 is related with lower susceptibility to dengue hemorrhagic fever.…”

Section: Introductionmentioning

confidence: 99%

Is there any relationship between Toll‐like receptor 3 c.1377C/T and −7C/A polymorphisms and susceptibility to Crimean Congo hemorrhagic fever?

Engin

Arslan

Özbilüm

et al. 2016

Journal of Medical Virology

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Crimean-Congo hemorrhagic fever (CCHF) is an infectious disease that is caused by CCHF virus. A family of transmembrane receptors called as Toll-like receptors (TLRs) selectively acts in recognizing a wide range of microbial components and endogenous molecules released by damaged tissue and have been preserved throughout evolution. TLRs initiate some signaling cascades which activate the innate immune system. Mainly four TLRs act in protection against viral infections; TLR3 is one of them. TLR3 identifies dsRNA. By producing inflammatory cytokines and type I interferons, it generates an antiviral immune response. Proper response to TLR ligands may be impaired by single nucleotide polymorphisms (SNPs) within TLR genes in some indviduals, and this can cause varied susceptibility to infections. In the present work, polymerase chain reaction-based restriction fragment length polymorphism is used to analyze the frequencies of TLR3 (c.1377C/T and -7C/A) polymorphisms in 149 CCHF patients and 171 healthy adults as controls, in Cumhuriyet University, Sivas/Turkey. We also investigated the relation between these polymorphisms and severity or mortality of CCHF disease. This is the first study investigating the TLR3 SNPs in patients with CCHF. In the present study, the frequency of the TLR3 (c.1377C/T and -7A/C) genotypes in fatal and non-fatal cases were comparable, however, the homozygous mutant (TT) genotype frequency of TLR3 c.1377C/T in CCHF patients was significantly higher than that of the healthy controls. In conclusion, presence of TLR3 c.1377 TT genotype may have a role in the susceptibility to CCHF. J. Med. Virol. 88:1690-1696, 2016. © 2016 Wiley Periodicals, Inc.

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Polymorphisms in RNA sensing toll like receptor genes and its association with clinical outcomes of dengue virus infection

Cited by 22 publications

References 24 publications

Association of Genetic Polymorphisms in TLR3, TLR4, TLR7, and TLR8 with the Clinical Forms of Dengue in Patients from Veracruz, Mexico

Association of Genetic Polymorphisms in TLR3, TLR4, TLR7, and TLR8 with the Clinical Forms of Dengue in Patients from Veracruz, Mexico

TLR8 Couples SOCS-1 and Restrains TLR7-Mediated Antiviral Immunity, Exacerbating West Nile Virus Infection in Mice

Is there any relationship between Toll‐like receptor 3 c.1377C/T and −7C/A polymorphisms and susceptibility to Crimean Congo hemorrhagic fever?

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