Susceptibility to HIV‐1 infection is influenced by toll like receptor‐2 (−196 to −174) polymorphism in a north Indian population

Vidyant, Sanjukta; Chatterjee, Animesh; Agarwal, Vikas; Dhole, Tapan N.

doi:10.1002/jgm.2971

Cited by 10 publications

(12 citation statements)

References 53 publications

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“…TLR2 Del homozygous genotype may be associated with reduced risk of HIV-1 disease progression. [ 51 ] The results of TLR2 (rs5743708, rs5743704) were same as Soriano-Sarabia et al results. [ 43 ] The remaining results of the Vidyant study pointed out TLR4 rs4986790 is associated with stage progression, but not observed in TLR4 rs4986791.…”

Section: Resultssupporting

confidence: 80%

“…The study performed on an Indian cohort indicated that TLR2 –196 to –174 Ins/Del polymorphism is a risk factor for HIV-1 infection. [ 51 ] Compared with healthy controls, TLR2 Del mutant genotype (OR = 2.138; P = .001) and allele (OR = 1.562; P = .002) was higher in patients with HIV-1 infection. This correlation did not find in other TLR2 genes (rs5743708, rs5743704, rs12191786).…”

Section: Resultsmentioning

confidence: 99%

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Association of toll-like receptor polymorphisms with acquisition of HIV infection and clinical findings

Shi

Sun³

et al. 2020

Medicine

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Background: To find the relationship between toll-like receptor (TLR) gene variants and human immunodeficiency virus (HIV) infection and clinical findings, which could inform clinical decisions and vaccination strategies. Method: Four databases were searched for articles that were published on or before Jul.1, 2020. Review Manager 5.3 software was applied to perform meta-analysis to explore. Results: A total of 10 studies involving 20 genes, 3697 cases, and 6498 controls were included in this systematic review. TLR2 –196 to –174 Ins/Del (odds ratio [OR] = 1.562; P = .002), TLR4 rs4986790 (OR = 2.05; P = .002), TLR3 rs3775291 (OR = 0.25; P = .03), TLR7 rs179008 ( P = .002), TLR7 rs2074109 (OR = 0.27, P = .019) were found associated with HIV infection. TLR2 –196 to –174, TLR4 rs4986790, TLR7 rs179008, TLR8 rs3764880, TLR9 rs352140 were found associated with clinical findings of HIV infection. We identified 5 case-control studies in meta-analysis, involving 695 cases and 729 controls on TLR7 rs179008 polymorphism, totaling 652 cases and 614 controls on TLR9 rs352140 polymorphism. In meta-analysis, we employed various genetic models. The T allele of TLR7 rs179008 was conferred the risk of HIV infection (T vs A: OR = 1.25, P A = .02). An increased risk of HIV infection was found for individuals with the TLR9 rs352140 GG genotype (GG vs AA: OR = 1.50, P A = .04). Conclusions: The systematic review indicated that TLR7 rs179008 T allele provides risk effects for HIV infection. TLR9 rs352140 GG genotype may associate with HIV infection.

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Section: Resultssupporting

confidence: 80%

Section: Resultsmentioning

confidence: 99%

Association of toll-like receptor polymorphisms with acquisition of HIV infection and clinical findings

Shi

Sun³

et al. 2020

Medicine

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“…Regardless of malaria contributing to positive selection and emergence of 'ins' allele of TLR2 gene in higher primates, the observation that humans with 'del' allele are prone to increased TLR2 mediated inflammation has opened up avenues for future investigations on innate immunity/ inflammation in humans. Both innate as well as adaptive immune responses are directly influenced by TLR-2 mediated activation of dendritic cells and T lymphocytes [32][33][34] and thus 'ins' vs 'del' in TLR2 gene could influence host response and susceptibility of humans to several other diseases such as HIV-AIDS 35 , H. pylori mediated gastric cancer 36 and Alzheimer's disease 37 .…”

Section: Discussionmentioning

confidence: 99%

A primate specific loss of function polymorphism in TLR2 gene decreases inflammation and protects humans from organ dysfunction in Malaria

Mukherjee

Tripathy

Sharma

et al. 2017

Preprint

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Polymorphisms of TLR genes could regulate and contribute functionally to innate immunity and inflammation. TLR2, a promiscous receptor recognizes Pathogen Associated Molecular Patterns from several microbes, bacterial, viral, protozoan and helminths. We demonstrate that monocytes of humans with deletion polymorphism in TLR2 gene (a 23 bp deletion in 5’ UTR region) respond more vigorously in vitro to several TLR2 ligands in comparison to those with insertion allele. Lower primates such as Rhesus monkeys and Baboon display ‘deletion’ genotype while insertion is found in higher primates viz., Orangutan, Chimpanzees and Gorilla. Enhanced inflammation is a hallmark of pathogenesis in human severe malaria leading to bad prognosis and odds ratio of patients prone to develop severe malaira such as multi organ failure with del/del genotype was found to be very high. Based on induction of inflammatory cytokines by normal human PBMCs in vitro and circulating cytokine levels in cohorts of patients with severe P. falciparum malaria, we propose that ‘insertion’ of a 23bp sequence in 5’UTR region of TLR2 gene could have led to moderated TLR2 induced inflammation thus offering survival advantage to higher primates by rendering them relatively refractory to multi-organ dysfunction in severe malaria.One Sentence SummaryA 23bp deletion in TLR2 gene is associated with high inflammation and susceptibility to organ dysfunction in Plasmodium falciparum malaria.

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“…Infection of TLR2 knockout mice with Friend virus (FV), a gammaretrovirus, revealed no impact on viral loads or immunity (E Browne unpublished observation), but genetic evidence from humans has indicated a possible role for TLR2 in HIV infection and disease progression. Specifically, a deletion allele of TLR2 (−196 to −174 Ins/Del) is associated with elevated risk of HIV infection and faster disease progression [51,52]. The mechanism behind how this genetic variant impacts HIV infection is still unclear.…”

Section: Tlr2mentioning

confidence: 99%

The Role of Toll-Like Receptors in Retroviral Infection

Browne

2020

Microorganisms

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Toll-like receptors (TLRs) are key pathogen sensing receptors that respond to diverse microbial ligands, and trigger both innate and adaptive immune responses to infection. Since their discovery, a growing body of evidence has pointed to an important role for TLRs in retroviral infection and pathogenesis. These data suggest that multiple TLRs contribute to the anti-retroviral response, and that TLR engagement by retroviruses can have complex and divergent outcomes for infection. Despite this progress, numerous questions remain about the role of TLRs in retroviral infection. In this review, I summarize existing evidence for TLR-retrovirus interactions and the functional roles these receptors play in immunity and pathogenesis, with particular focus on human immunodeficiency virus (HIV).

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Susceptibility to HIV‐1 infection is influenced by toll like receptor‐2 (−196 to −174) polymorphism in a north Indian population

Abstract: The present study reports for the first time that the TLR2-196 to -174 Ins/Del polymorphism is a risk factor for HIV-1 transmission in HIV-1 infected North Indian individuals.

Cited by 10 publications

References 53 publications

Association of toll-like receptor polymorphisms with acquisition of HIV infection and clinical findings

Association of toll-like receptor polymorphisms with acquisition of HIV infection and clinical findings

A primate specific loss of function polymorphism in TLR2 gene decreases inflammation and protects humans from organ dysfunction in Malaria

The Role of Toll-Like Receptors in Retroviral Infection

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