The severity of SARS-CoV-2 infection is dictated by host factors? Epigenetic perspectives

Sethumadhavan, Devadathan Valiyamangalath; Jabeena, C. A.; Govindaraju, Gayathri; Soman, Aparna; Rajavelu, Arumugam

doi:10.1016/j.crmicr.2021.100079

Cited by 4 publications

(2 citation statements)

References 147 publications

(206 reference statements)

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“…In our study, all DNMTs were inversely correlated with COVID-19 disease, whereas DNMT1 and DNMT3A, but not DNMT3B, had an inverse relationship with disease severity. It was found that the oxidative stress induced by SARS-CoV-2 infection led to inhibition of DNMT1 and alteration of DNA methylation [ 18 ]. In addition, we found that DNMT1, DNMT3A, and DNMT3B expression were positively correlated.…”

Section: Discussionmentioning

confidence: 99%

Altered expression of DNA methyltransferases and methylation status of the TLR4 and TNF-α promoters in COVID-19

et al. 2023

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Epigenetic modifications play a significant role in the host's immune response to viral infection. Two epigenetic events, DNA methylation and histone acetylation, are crucial for modifying the chromatin architecture and the location of regulatory elements such as promoters and enhancers. In this case-control study, we evaluated the expression of genes involved in epigenetic machinery (DNMT1, DNMT3A, DNMT3B, HDAC2, and HDAC3) and the degree of methylation of promoters of immune response genes (IFITM1/2/3, TLR3/4, TNF-α, NF-κB, and MYD88) as well as global methylation (LINE-1 and global 5–mC) in blood samples from 120 COVID-19 patients (30 mild, 30 moderate, 30 severe, and 30 critical) and 30 healthy subjects without COVID-19. In contrast to previous reports, DNMT3A and DNMT3B expression was found to be significantly downregulated in COVID-19 cases, whereas DNMT1, HDAC2, and HDAC3 expression did not change. DNMT1 and DNMT3A were negatively correlated with COVID-19 severity. Critically ill patients had lower HDAC3 expression levels. TLR4 and TNF-α had increased promoter methylation, whereas IFITM1/2/3, TLR3, NF-κB, MYD88, and LINE-1 did not differ between cases and controls. Methylation of the TNF-α promoter increased as disease severity increased. Significantly less methylation of the TLR3 promoter was observed in patients with a positive outcome (recovery). We also found a correlation between the expression of DNMT3B and the methylation level of the TLR4 promoter. In milder cases, the global 5–mC levels were lower than that in more severe cases. Our findings suggest the exclusion of DNMTs inhibitors previously recommended for COVID-19 treatment and the need for additional research in this area.

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Section: Discussionmentioning

confidence: 99%

Altered expression of DNA methyltransferases and methylation status of the TLR4 and TNF-α promoters in COVID-19

et al. 2023

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“…Furthermore, in lung diseases, ACE2 is overexpressed but is regulated by histone acetyltransferases and histone lysine deacetylases, from the attenuation of the chromatin structure, in addition to DNA hypomethylation, in the ACE2 gene locus. 91,92 It was also evident that the severity of COVID-19 correlates to the existence of previous pulmonary conditions of an individual. In this sense, studies have revealed that gene loci are associated with both lung diseases (such as interstitial lung disease, lung fibrosis, lung carcinomas, and decreased lung function) and the severity of SARS-CoV-2 infection.…”

Section: Lung Diseasesmentioning

confidence: 99%

Host Genetics and COVID-19: Genes Underlying the Patterns of Susceptibility and Prognosis

Khouri,

de Souza Candido,

Poli-Frederico

et al. 2023

Gene Expr

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Host-specific genetics, such as epigenetic profiles and genetic variants, can contribute to the pathogenesis of infectious diseases. Strong associations have been previously identified in infections by human immunodeficiency virus (HIV), Plasmodium falciparum, norovirus, and influenza A virus. Despite the efforts to characterize the role of host genetics in severe acute respiratory syndrome virus coronavirus 2 (SARS-CoV-2) infection, this comprehension remains incipient. Coronavirus disease 2019 (COVID-19) can evolve with a wide spectrum of manifestations, ranging from asymptomatic and mild cases to severe forms with acute respiratory distress syndrome, multi-organ complications, and even death. Classic clinical risk factors only partially explain this interindividual variability, suggesting that host genetics may contribute to the heterogeneity of courses. Robust evidence has revealed the multiple associations of genes (ABO,

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Influence of environmental and demographic factors on the transmission and mortality rate of COVID19 in India

Kalidoss¹,

Patil²,

Misra³

et al. 2023

Proceeding of International Conference on Energy, Manufacture, Advanced Material and Mechatronics 2021

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The severity of SARS-CoV-2 infection is dictated by host factors? Epigenetic perspectives

Cited by 4 publications

References 147 publications

Altered expression of DNA methyltransferases and methylation status of the TLR4 and TNF-α promoters in COVID-19

Altered expression of DNA methyltransferases and methylation status of the TLR4 and TNF-α promoters in COVID-19

Host Genetics and COVID-19: Genes Underlying the Patterns of Susceptibility and Prognosis

Influence of environmental and demographic factors on the transmission and mortality rate of COVID19 in India

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