microRNA, the Innate-Immune System and SARS-CoV-2

Abstract

The single-stranded viral RNA (ssvRNA) known as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes COVID-19 can be effectively inactivated by a number of natural ribonucleic acid-based host cell defenses. One of the most important of these defenses includes the actions of a class of small non-coding RNAs (sncRNAs) known as microRNAs (miRNAs). Via base-pair complementarity miRNAs are capable of specifically targeting ssvRNA sequences such as SARS-CoV-2 promoting its inactivation and neutralization. RNA-sequencing and bioinformatics analysis indicate that multiple naturally-occurring human miRNAs have extensive complementarity to the SARS-CoV-2 ssvRNA genome. Since miRNA abundance, speciation, and complexity vary significantly amongst human individuals, this may in part explain the variability in the innate-immune and pathophysiological response of different individuals to SARS-CoV-2 and overall susceptibility to ssvRNA-mediated viral infection.

MicroRNA-155 and 194 alter expression of Th17 and T regulatory-related transcription factors in the patients with severe coronavirus disease 2019 (COVID-19)

“…Among the microRNAs, some molecules can be considered as important regulators of SARS-CoV-2 gene expression and also expression of T-bet, GATA3, RORγt, and FOXP3 transcription factors and their products ( Liang and Tang, 2020 ). The roles played by microRNAs in the pathogenesis of COVID-19 were also confirmed by several investigations ( Hill and Lukiw, 2022 , Cuț et al, 2022 ). For example, microRNAs can regulate the immune cell functions and can also be used as potential biomarkers ( Azhar, et al, 2022 ).…”

SARS-CoV-2 Neuroinvasion, Inflammatory Neurodegeneration and Alzheimer's Disease

“…′ methyl cap structure, a 3 ′ poly(A) tail and ∼10-14 overlapping open reading frames (ORFs) with minimal spacer regions, encoding about ∼30 proteins, not all of which have been fully characterized (Ke et al, 2020;Sah et al, 2020;Raghuvamsi et al, 2021). SARS-CoV-2 is highly neurotropic toward cells and tissues of the brain, visual system and CNS (Song et al, 2020;Hill et al, 2021;Zhao et al, 2021;Lukiw, 2022a) and orchestrates a highly coordinated and multipronged strategy to impede host protein synthesis including the accelerated degradation of host cytosolic cellular mRNAs, thus facilitating viral takeover of the host mRNA pool in infected cells (Hosseini et al, 2021;Hill and Lukiw, 2022;Lukiw et al, 2022). As a ssRNA virus SARS-CoV-2 is representative of the most common type of emerging viral disease in humans (due to the high mutation rate in RNA compared to DNA viruses) that possess extremely high mutation rates of up to 10 6 times higher than that of their host cells (Pachetti et al, 2020;Finkel et al, 2021).…”

“…This 'S1' protein is a class 1 homo-trimeric viral fusion protein possessing distinctive 'head' and 'stalk' domains essential for host cell entry via the ACE2R (see below; Ke et al, 2020;Lukiw, 2021;Raghuvamsi et al, 2021). Interestingly SARS-CoV-2 possesses one of the largest genomes of all known ssRNA neurotropic viruses and a correspondingly large target for potential interaction with natural cellular sncRNA and miRNA (Finkel et al, 2021;Mousavizadeh and Ghasemi, 2021;Hill and Lukiw, 2022).…”

“…For example, increases in the proinflammatory NF-kB (p50/p65)-inducible miRNA-146a and miRNA-155, significantly up-regulated in AD-and prionaffected brain and CNS and implicated in pathological disruption of the innate-immune system, altered microglial-regulated wasteproduct clearance and complement factor H (CFH)-mediated complement activation, most often accompanies the viral-, bacterial-and other microbial-mediated infections of all brain cells and tissues examined to date (Slota and Booth, 2019;Li et al, 2021;Pogue and Lukiw, 2021;Azhar et al, 2022;Choe et al, 2022;Kucher et al, 2022;Maranini et al, 2022;Pogue et al, 2022). Importantly, the abundance, speciation and complexity of miRNA populations varies considerably in the individual human host and because miRNAs can target and inactivate ssRNA viruses such as H1N1/H3N2, Zika virus and SARS-CoV-2 may help to explain individual heterogeneity in the susceptibility to systemic attack and infection by human ssRNA viruses (Azhar et al, 2022;Hill and Lukiw, 2022;Kucher et al, 2022).…”

“…These intrinsic SARCoV-2 parameters would therefore down-regulate, deplete and disrupt the abundance and natural levels of free miRNAs within the cell creating metabolic and signaling instability in brain cells while supporting neuro-inflammation and AD-type change (SARS-CoV-2 isolate Wuhan-Hu-1, National Center for Biological Information (NCBI) GenBank Accession No. NC_045512.2; last accessed 27 May 2022; Ke et al, 2020;Sah et al, 2020;Wu et al, 2020;Mousavizadeh and Ghasemi, 2021;Hill and Lukiw, 2022).…”