Epigenetic susceptibility to severe respiratory viral infections: pathogenic and therapeutic implications: a narrative review
Date
2020Author
Crimi, Ettore
Benincasa, Giuditta
Figueroa-Marrero, Neisaliz
Galdiero, Massimiliano
Napoli, Claudio
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Abstract
The emergence of highly pathogenic strains of influenza virus and coronavirus (CoV) has been responsible for large
epidemic and pandemic outbreaks characterised by severe pulmonary illness associated with high morbidity and
mortality. One major challenge for critical care is to stratify and minimise the risk of multi-organ failure during the stay
in the intensive care unit (ICU). Epigenetic-sensitive mechanisms, including deoxyribonucleic acid (DNA) and ribonucleic
acid (RNA) methylation, histone modifications, and non-coding RNAs may lead to perturbations of the host immunerelated transcriptional programmes by regulating chromatin structure and gene expression patterns. Viruses causing
severe pulmonary illness can use epigenetic-regulated mechanisms during hostepathogen interaction to interfere with
innate and adaptive immunity, adequacy of inflammatory response, and overall outcome of viral infections. For
example, Middle East respiratory syndrome-CoV and H5N1 can affect host antigen presentation through DNA methylation and histone modifications. The same mechanisms would presumably occur in patients with coronavirus disease
2019, in which tocilizumab may epigenetically reduce microvascular damage. Targeting epigenetic pathways by immune
modulators (e.g. tocilizumab) or repurposed drugs (e.g. statins) may provide novel therapeutic opportunities to control
viralehost interaction during critical illness. In this article, we provide an update on epigenetic-sensitive mechanisms
and repurposed drugs interfering with epigenetic pathways which may be clinically suitable for risk stratification and
beneficial for treatment of patients affected by severe viral respiratory infections.
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https://doi.org/10.1016/j.bja.2020.06.060Collections
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