ABSTRACT
COVID-19 induces chromatin remodeling in host immune cells, and it had previously been shown that vitamin B12 downregulates some inflammatory genes via methyl-dependent epigenetic mechanisms. In this work, whole blood cultures from moderate or severe COVID-19 patients were used to assess the potential of B12 as adjuvant drug. The vitamin normalized the expression of a panel of inflammatory genes still dysregulated in the leukocytes despite glucocorticoid therapy during hospitalization. B12 also increased the flux of the sulfur amino acid pathway, that regulates the bioavailability of methyl. Accordingly, B12-induced downregulation of CCL3 strongly and negatively correlated with the hypermethylation of CpGs in its regulatory regions. Transcriptome analysis revealed that B12 attenuates the effects of COVID-19 on most inflammation-related pathways affected by the disease. As far as we are aware, this is the first study to demonstrate that pharmacological modulation of epigenetic markings in leukocytes favorably regulates central components of COVID-19 physiopathology.
Subject(s)
COVID-19 , Vitamin B 12 , Humans , Vitamin B 12/pharmacology , Vitamin B 12/metabolism , DNA Methylation , Epigenesis, Genetic , Leukocytes/metabolismABSTRACT
Emerging life-threatening viruses have posed great challenges to public health. It is now increasingly clear that epigenetics plays a role in shaping host-virus interactions and there is a great need for a more thorough understanding of these intricate interactions through the epigenetic lens, which may represent potential therapeutic opportunities in the clinic. In this review, we highlight the current understanding of the roles of key epigenetic regulators - chromatin remodeling and histone modification - in modulating chromatin openness during host defense against virus. We also discuss how the RNA modification m6A (N6-methyladenosine) affects fundamental aspects of host-virus interactions. We conclude with future directions for uncovering more detailed functions that epigenetic regulation exerts on both host cells and viruses during infection.
Subject(s)
Antiviral Agents/immunology , Epigenesis, Genetic/genetics , Epigenesis, Genetic/immunology , Immunity, Innate/genetics , Immunity, Innate/immunology , Animals , Chromatin/genetics , Chromatin/immunology , Histones/genetics , Histones/immunology , Host Microbial Interactions/genetics , Host Microbial Interactions/immunology , Humans , RNA Processing, Post-Transcriptional/genetics , RNA Processing, Post-Transcriptional/immunologyABSTRACT
COVID-19 pandemic waves hitting worldwide result in drastic postinfection complications with interindividual variations, which raised the question for the cause of these observed variations. This urged to think "the impact of environment-affected genes"? In an attempt to unravel the impact of environment-affected genes, a systematic rapid review was conducted to study "the impact of host or viral epigenetic modulation on COVID-19 infection susceptibility and/or outcome." Electronic databases including Web of Science, SCOPUS, Cochrane Central Register of Controlled Trials, PubMed, and Google Scholar, and other databases were searched. The search strings included "COVID-19" OR "SARS-CoV-2" AND (Epigenetics'). Articles with randomized clinical trials (RCTs) and observational study designs, conducted on humans and available in the English language, were selected, with respect to "The interplay between the SARS-CoV-2 virus and Epigenetics" published from 2020 to February 2021 (but not limited to 2020, being expanded to 2015). Database search yielded 1330 articles; after screening, exclusion, and further filtrations, 51 articles were included. Susceptibility to COVID-19 infection is related to the viral-microRNAs (miRNAs) which alter virulence of the transmitted SARS-CoV-2 strains and impact host-miRNA-related innate immunity. Host-DNA methylation and/or chromatin remodeling may be implicated in severe cytokine storm that can ultimately results in fatal outcome.