Association of TLR3 functional variant (rs3775291) with COVID-19 susceptibility and death: a population-scale study

Dhangadamajhi, Gunanidhi; Rout, Ronnaly

doi:10.1007/s13577-021-00510-6

Cited by 25 publications

(18 citation statements)

References 14 publications

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“…Thus, TLR-3 deficiency is associated with high susceptibility to RNA virus infection, and the deficiency or mutation of the rs3775291 polymorphism prevents its expression and is also associated with diabetes and pulmonary hypertension. This leads to a rapid progression of COVID-19 in infected patients [15,184].…”

Section: Polymorphisms In Tlr and Their Signaling Moleculesmentioning

confidence: 99%

“…No data reported. rs3775291 and rs3775290 [14,15,183,185]. Other variants are p.Ser339fs, p.Pro554Ser, p.Trp769*, and p.Met870Val [17].…”

Section: Tyk2mentioning

confidence: 99%

“…As some examples of PRRs, we can mention polymorphisms of Toll-like receptor (TLR)-3 or molecules involved in their signaling pathways [14][15][16] as well as polymorphisms of RIG-1 and MDA5, which are associated with susceptibility to SARS-CoV-2 infection due to lack for recognition of viral RNA and disrupted signaling pathway for IFN production.…”

Section: Introductionmentioning

confidence: 99%

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Implications of the Immune Polymorphisms of the Host and the Genetic Variability of SARS-CoV-2 in the Development of COVID-19

Zepeda–Cervantes

Martínez-Flores

Ramírez-Jarquín

et al. 2022

Viruses

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The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for the current pandemic affecting almost all countries in the world. SARS-CoV-2 is the agent responsible for coronavirus disease 19 (COVID-19), which has claimed millions of lives around the world. In most patients, SARS-CoV-2 infection does not cause clinical signs. However, some infected people develop symptoms, which include loss of smell or taste, fever, dry cough, headache, severe pneumonia, as well as coagulation disorders. The aim of this work is to report genetic factors of SARS-CoV-2 and host-associated to severe COVID-19, placing special emphasis on the viral entry and molecules of the immune system involved with viral infection. Besides this, we analyze SARS-CoV-2 variants and their structural characteristics related to the binding to polymorphic angiotensin-converting enzyme type 2 (ACE2). Additionally, we also review other polymorphisms as well as some epigenetic factors involved in the immunopathogenesis of COVID-19. These factors and viral variability could explain the increment of infection rate and/or in the development of severe COVID-19.

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Section: Polymorphisms In Tlr and Their Signaling Moleculesmentioning

confidence: 99%

“…No data reported. rs3775291 and rs3775290 [14,15,183,185]. Other variants are p.Ser339fs, p.Pro554Ser, p.Trp769*, and p.Met870Val [17].…”

Section: Tyk2mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Implications of the Immune Polymorphisms of the Host and the Genetic Variability of SARS-CoV-2 in the Development of COVID-19

Zepeda–Cervantes

Martínez-Flores

Ramírez-Jarquín

et al. 2022

Viruses

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“…preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in The copyright holder for this this version posted March 26, 2021. ; https://doi.org/10.1101/2021.03. 23.21254158 doi: medRxiv preprint also leads to poor recognition of SARS-CoV-2 dsRNA compared to its wild type counterpart [9] and has been recently associated with SARS-CoV-2 susceptibility and mortality [10].…”

Section: Introductionmentioning

confidence: 99%

“…Among TLR3 variants, the functional L412F polymorphism (rs3775291; c.1234C>T) is known to decrease TLR3 expression on the cell surface [8]. This polymorphism also leads to poor recognition of SARS-CoV-2 dsRNA compared to its wild type counterpart [9] and has been recently associated with SARS-CoV-2 susceptibility and mortality [10].…”

Section: Introductionmentioning

confidence: 99%

The polymorphism L412F in TLR3 inhibits autophagy and is a marker of severe COVID-19 in males

Croci

Venneri

Mantovani

et al. 2021

Preprint

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The polymorphism L412F in TLR3 has been associated with several infectious diseases. However, the mechanism underlying this association is still unexplored. Here, we show that the L412F polymorphism in TLR3 is a marker of severity in COVID-19. This association increases in the sub-cohort of males. Impaired autophagy and reduced TNFα production was demonstrated in HEK293 cells transfected with TLR3-L412F plasmid and stimulated with specific agonist poly(I:C). A statistically significant reduced survival at 28 days was shown in L412F COVID-19 patients treated with the autophagy-inhibitor hydroxychloroquine (P=0.038). An increased frequency of autoimmune disorders as co-morbidity was found in L412F COVID-19 males with specific class II HLA haplotypes prone to autoantigen presentation. Our analyses indicate that L412F polymorphism makes males at risk of severe COVID-19 and provides a rationale for reinterpreting clinical trials considering autophagy pathways.

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Toll-Like Receptors (TLRs) in Health and Disease: An Overview

Kumar

Barrett

2022

Handbook of Experimental Pharmacology

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Association of TLR3 functional variant (rs3775291) with COVID-19 susceptibility and death: a population-scale study

Cited by 25 publications

References 14 publications

Implications of the Immune Polymorphisms of the Host and the Genetic Variability of SARS-CoV-2 in the Development of COVID-19

Implications of the Immune Polymorphisms of the Host and the Genetic Variability of SARS-CoV-2 in the Development of COVID-19

The polymorphism L412F in TLR3 inhibits autophagy and is a marker of severe COVID-19 in males

Toll-Like Receptors (TLRs) in Health and Disease: An Overview

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