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Endogenous miRNA-Based Innate-Immunity against SARS-CoV-2 Invasion of the Brain

The severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2), the causative agent of COVID-19, possesses an unusually large positive-sense, single-stranded viral RNA (ssvRNA) genome of about ~29,903 nucleotides (nt). In many respects, this ssvRNA resembles a very large, polycistronic messenger R...

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Autores principales: Lukiw, Walter J., Pogue, Aileen I.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9966119/
https://www.ncbi.nlm.nih.gov/pubmed/36834773
http://dx.doi.org/10.3390/ijms24043363
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author Lukiw, Walter J.
Pogue, Aileen I.
author_facet Lukiw, Walter J.
Pogue, Aileen I.
author_sort Lukiw, Walter J.
collection PubMed
description The severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2), the causative agent of COVID-19, possesses an unusually large positive-sense, single-stranded viral RNA (ssvRNA) genome of about ~29,903 nucleotides (nt). In many respects, this ssvRNA resembles a very large, polycistronic messenger RNA (mRNA) possessing a 5′-methyl cap (m(7)GpppN), a 3′- and 5′-untranslated region (3′-UTR, 5′-UTR), and a poly-adenylated (poly-A+) tail. As such, the SARS-CoV-2 ssvRNA is susceptible to targeting by small non-coding RNA (sncRNA) and/or microRNA (miRNA), as well as neutralization and/or inhibition of its infectivity via the human body’s natural complement of about ~2650 miRNA species. Depending on host cell and tissue type, in silico analysis, RNA sequencing, and molecular-genetic investigations indicate that, remarkably, almost every single human miRNA has the potential to interact with the primary sequence of SARS-CoV-2 ssvRNA. Individual human variation in host miRNA abundance, speciation, and complexity among different human populations and additional variability in the cell and tissue distribution of the SARS-CoV-2 angiotensin converting enzyme-2 (ACE2) receptor (ACE2R) appear to further contribute to the molecular-genetic basis for the wide variation in individual host cell and tissue susceptibility to COVID-19 infection. In this paper, we review recently described aspects of the miRNA and ssvRNA ribonucleotide sequence structure in this highly evolved miRNA–ssvRNA recognition and signaling system and, for the first time, report the most abundant miRNAs in the control superior temporal lobe neocortex (STLN), an anatomical area involved in cognition and targeted by both SARS-CoV-2 invasion and Alzheimer’s disease (AD). We further evaluate important factors involving the neurotropic nature of SARS-CoV-2 and miRNAs and ACE2R distribution in the STLN that modulate significant functional deficits in the brain and CNS associated with SARS-CoV-2 infection and COVID-19’s long-term neurological effects.
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spelling pubmed-99661192023-02-26 Endogenous miRNA-Based Innate-Immunity against SARS-CoV-2 Invasion of the Brain Lukiw, Walter J. Pogue, Aileen I. Int J Mol Sci Review The severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2), the causative agent of COVID-19, possesses an unusually large positive-sense, single-stranded viral RNA (ssvRNA) genome of about ~29,903 nucleotides (nt). In many respects, this ssvRNA resembles a very large, polycistronic messenger RNA (mRNA) possessing a 5′-methyl cap (m(7)GpppN), a 3′- and 5′-untranslated region (3′-UTR, 5′-UTR), and a poly-adenylated (poly-A+) tail. As such, the SARS-CoV-2 ssvRNA is susceptible to targeting by small non-coding RNA (sncRNA) and/or microRNA (miRNA), as well as neutralization and/or inhibition of its infectivity via the human body’s natural complement of about ~2650 miRNA species. Depending on host cell and tissue type, in silico analysis, RNA sequencing, and molecular-genetic investigations indicate that, remarkably, almost every single human miRNA has the potential to interact with the primary sequence of SARS-CoV-2 ssvRNA. Individual human variation in host miRNA abundance, speciation, and complexity among different human populations and additional variability in the cell and tissue distribution of the SARS-CoV-2 angiotensin converting enzyme-2 (ACE2) receptor (ACE2R) appear to further contribute to the molecular-genetic basis for the wide variation in individual host cell and tissue susceptibility to COVID-19 infection. In this paper, we review recently described aspects of the miRNA and ssvRNA ribonucleotide sequence structure in this highly evolved miRNA–ssvRNA recognition and signaling system and, for the first time, report the most abundant miRNAs in the control superior temporal lobe neocortex (STLN), an anatomical area involved in cognition and targeted by both SARS-CoV-2 invasion and Alzheimer’s disease (AD). We further evaluate important factors involving the neurotropic nature of SARS-CoV-2 and miRNAs and ACE2R distribution in the STLN that modulate significant functional deficits in the brain and CNS associated with SARS-CoV-2 infection and COVID-19’s long-term neurological effects. MDPI 2023-02-08 /pmc/articles/PMC9966119/ /pubmed/36834773 http://dx.doi.org/10.3390/ijms24043363 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Lukiw, Walter J.
Pogue, Aileen I.
Endogenous miRNA-Based Innate-Immunity against SARS-CoV-2 Invasion of the Brain
title Endogenous miRNA-Based Innate-Immunity against SARS-CoV-2 Invasion of the Brain
title_full Endogenous miRNA-Based Innate-Immunity against SARS-CoV-2 Invasion of the Brain
title_fullStr Endogenous miRNA-Based Innate-Immunity against SARS-CoV-2 Invasion of the Brain
title_full_unstemmed Endogenous miRNA-Based Innate-Immunity against SARS-CoV-2 Invasion of the Brain
title_short Endogenous miRNA-Based Innate-Immunity against SARS-CoV-2 Invasion of the Brain
title_sort endogenous mirna-based innate-immunity against sars-cov-2 invasion of the brain
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9966119/
https://www.ncbi.nlm.nih.gov/pubmed/36834773
http://dx.doi.org/10.3390/ijms24043363
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