COVID-19 susceptibility, severity, clinical outcome and Toll-like receptor (7) mRNA expression driven by TLR7 gene polymorphism (rs3853839) in middle-aged individuals without previous comorbidities

El-Hefnawy, Sally M; Eid, Hanaa A.; Mostafa, Rasha G.; Soliman, Shaimaa; Omar, Thoria Ahmed; Azmy, Rania

doi:10.1016/j.genrep.2022.101612

Cited by 15 publications

(20 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Additionally, TLR7 mRNA expression levels were significantly higher among patients, particularly among those with GG genotype (rs3853839). Moreover, significantly lower WBC but higher IL6, CRP, and ferritin levels were observed among patients 97 . Therefore, these SNPs were correlated with SARS‐COV‐2 infection, cytokine storm, and patients' higher mortality rates.…”

Section: Tlrs Genes Polymorphismsmentioning

confidence: 88%

“…Moreover, significantly lower WBC but higher IL6, CRP, and ferritin levels were observed among patients. 97 Therefore, these SNPs were correlated with SARS‐COV‐2 infection, cytokine storm, and patients' higher mortality rates. In addition, TLR9 rs352162, rs352162, and rs187084 SNPs were associated with HCV infection and ICU admission.…”

Section: Tlrs Genes Polymorphismsmentioning

confidence: 98%

See 1 more Smart Citation

Individual genetic variability mainly of Proinflammatory cytokines, cytokine receptors, and toll‐like receptors dictates pathophysiology of COVID‐19 disease

Vakil

Mansoori

Al-Awsi

et al. 2022

Journal of Medical Virology

View full text Add to dashboard Cite

Innate and acquired immunity responses are crucial for viral infection elimination. However, genetic variations in coding genes may exacerbate the inflammation or initiate devastating cytokine storms which poses severe respiratory conditions in coronavirus disease-19 (COVID-19). Host genetic variations in particular those related to the immune responses determine the patients' susceptibility and COVID-19 severity and pathophysiology. Gene polymorphisms such as single nucleotide polymorphisms (SNPs) of interferons, TNF, IL1, IL4, IL6, IL7, IL10, and IL17 predispose patients to the severe form of COVID-19 or severe acute respiratory syndrome coronavirus-2 (SARS-COV-2). These variations mainly alter the gene expression and cause a severe response by B cells, T cells, monocytes, neutrophils, and natural killer cells participating in a cytokine storm. Moreover, cytokines and chemokines SNPs are associated with the severity of COVID-19 and clinical outcomes depending on the corresponding effect. Additionally, genetic variations in genes encoding toll-like receptors (TLRs) mainly TLR3, TLR7, and TLR9 have been related to the COVID-19 severe respiratory symptoms. The specific relation of these mutations with the novel variants of concern (VOCs) infection remains to be elucidated. Genetic variations mainly within genes encoding proinflammatory cytokines, cytokine receptors, and TLRs predispose patients to COVID-19 disease severity. Understanding host immune gene variations associated with the SARS-COV-2 infection opens insights to control the pathophysiology of emerging viral infections.

show abstract

Section: Tlrs Genes Polymorphismsmentioning

confidence: 88%

Section: Tlrs Genes Polymorphismsmentioning

confidence: 98%

Individual genetic variability mainly of Proinflammatory cytokines, cytokine receptors, and toll‐like receptors dictates pathophysiology of COVID‐19 disease

Vakil

Mansoori

Al-Awsi

et al. 2022

Journal of Medical Virology

View full text Add to dashboard Cite

show abstract

“…The rs3853839 single nucleotide polymorphysm (SNP) of toll-like receptor 7 (TLR 7) can affect miRNA binding capacity and therefore mRNA expression of TLR7. The rs3853839 SNP, on the other hand, might pose a risk on the infection [56]. Conserved regions are predicted by miRanda and mirTarP as a conserved region of the virus.…”

Section: Identification Of Common Mirnas For Both Variantsmentioning

confidence: 99%

It isn t over ‘till it s over: A continuing concern of the SARS-CoV-2 variants, and miRNAs targeting the S protein as a probable absolute cure

Kilic¹,

Cosar²,

İnce³

et al. 2023

j-ebr

View full text Add to dashboard Cite

“…In particular, while it is understood that SARS-CoV2 utilized S-protein binding to ACE2 in order to enter cells, it is now increasingly reported that other pathways, involving innate immunity, may contribute to the inflammatory response. Viral genetic material activates TLR7, and there have been several reports linking TLR7 deficiency with severe outcomes in COVID19 (16; 69; 70). Less well understood is the role that S-protein-induced inflammation and cell injury may play in this disease.…”

Section: Introductionmentioning

confidence: 99%

The SARS-CoV-2 Spike S1 Protein Induces Global Proteomic Changes in ATII-Like Rat L2 Cells that are Attenuated by Hyaluronan

Mobley

Molyvdas

Kojima

et al. 2022

Preprint

View full text Add to dashboard Cite

The COVID-19 pandemic continues to impose a major impact on global health and economy since its identification in early 2020, causing significant morbidity and mortality worldwide. Caused by the SARS-CoV-2 virus, along with a growing number of variants that have been characterized to date, COVID-19 has led to 571,198,904 confirmed cases, and 6,387,863 deaths worldwide (as of July 15th, 2022). Despite tremendous advances in our understanding of COVID19 pathogenesis, the precise mechanism by which SARS-CoV2 causes epithelial injury is incompletely understood. In this current study, robust application of global-discovery proteomics applications combined with systems biology analysis identified highly significant induced changes by the Spike S1 protein of SARS-CoV-2 in an ATII-like Rat L2 cells that include three significant network hubs: E2F1, CREB1/ RelA, and ROCK2/ RhoA. Separately, we found that pre-treatment with High Molecular Weight Hyaluronan (HMW-HA), greatly attenuated the S1 effects. Immuno-targeted studies carried out on E2F1 and Rock2/ RhoA induction and kinase-mediated activation, in addition to cell cycle measurements, validated these observations. Taken as a whole, our discovery proteomics and systems analysis workflow, combined with standard immuno-targeted and cell cycle measurements revealed profound and novel biological changes that contribute to our current understanding of both Spike S1 and Hyaluronan biology. This data shows that the Spike S1 protein may contribute to epithelial injury induced by SARS-CoV-2. In addition, our work supports the potential benefit of HMW-HA in ameliorating SARS CoV2 induced cell injury.

show abstract

COVID-19 susceptibility, severity, clinical outcome and Toll-like receptor (7) mRNA expression driven by TLR7 gene polymorphism (rs3853839) in middle-aged individuals without previous comorbidities

Cited by 15 publications

References 40 publications

Individual genetic variability mainly of Proinflammatory cytokines, cytokine receptors, and toll‐like receptors dictates pathophysiology of COVID‐19 disease

Individual genetic variability mainly of Proinflammatory cytokines, cytokine receptors, and toll‐like receptors dictates pathophysiology of COVID‐19 disease

It isn t over ‘till it s over: A continuing concern of the SARS-CoV-2 variants, and miRNAs targeting the S protein as a probable absolute cure

The SARS-CoV-2 Spike S1 Protein Induces Global Proteomic Changes in ATII-Like Rat L2 Cells that are Attenuated by Hyaluronan

Contact Info

Product

Resources

About