Journal Article Review Epublish 1 citation
PubMed: 36834773 DOI: 10.3390/ijms24043363
Endogenous miRNA-Based Innate-Immunity against SARS-CoV-2 Invasion of the Brain.
Int J Mol Sci 24(4)
Authors: Walter J Lukiw, Aileen I Pogue
Affiliations
- LSU Neuroscience Center, Louisiana State University Health Science Center, New Orleans, LA 70112, USA.
- Alchem Biotech Research, Toronto, ON M5S 1A8, Canada.
- Department of Ophthalmology, LSU Health Science Center, New Orleans, LA 70112, USA.
- Department Neurology, Louisiana State University Health Science Center, New Orleans, LA 70112, USA.
Abstract
The severe acute respiratory syndrome -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 (mGpppN), 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.
MeSH
Infections, Brain, Cells, Immunity, Innate, Rna, Viral, Tissues, Cognition, Sars Virus, 5' Untranslated Regions, 3' Untranslated Regions, Micrornas, Rna, Messenger, Rna, Untranslated, Rna, Small Untranslated, Angiotensin-Converting Enzyme 2, Covid-19, Sars-Cov-2