Beauty and the beast: host microRNA-155 versus SARS-CoV-2

Abstract

Severe acute respiratory coronavirus 2 (SARS-CoV-2) infection in the young and healthy usually results in an asymptomatic or mild viral syndrome, possibly through an erythropoietin (EPO)-dependent, protective evolutionary landscape. In the old and in the presence of co-morbidities, however, a potentially lethal coronavirus disease 2019 (COVID-19) cytokine storm, through unrestrained renin-angiotensin aldosterone system (RAAS) hyperactivity, has been described. Multifunctional microRNA-155 (miR-155) elevation in malaria, dengue virus (DENV), the thalassemias, and SARS-CoV-1/2, plays critical antiviral and cardiovascular roles through its targeted translational repression of over 140 genes. In the present review, we propose a plausible miR-155-dependent mechanism whereby the translational repression of AGRT1 , Arginase-2 and Ets-1 , reshapes RAAS towards Angiotensin II (Ang II) type 2 (AT2R)-mediated balanced, tolerable, and SARS-CoV-2-protective cardiovascular phenotypes. In addition, it enhances EPO secretion and endothelial nitric oxide synthase activation and substrate availability, and negates proinflammatory Ang II effects. Disrupted miR-155 repression of AT1R + 1166C-allele, significantly associated with adverse cardiovascular and COVID-19 outcomes, manifests its decisive role in RAAS modulation. BACH1 and SOCS1 repression creates an anti-inflammatory and cytoprotective milieu, robustly inducing antiviral interferons. MiR-155 dysregulation in the elderly, and in comorbidities, allows unimpeded RAAS hyperactivity to progress towards a particularly aggressive COVID-19 course. Elevated miR-155 in thalassemia plausibly engenders a favorable cardiovascular profile and protection against malaria, DENV, and SARS-CoV-2. MiR-155 modulating pharmaceutical approaches could offer novel therapeutic options in COVID-19.

Vaccination increased host antiviral gene expression and reduced COVID-19 severity during the Omicron variant outbreak in Fuyang City, China

“…MicroRNAs play an important role in host antiviral immunity, and miRNAs have been reported as possible biomarkers in COVID-19 disease progression [36] , [37] , [38] , [39] . MiR-155 is a multifunctional microRNA that has an indispensable capacity in immune responses [40] , [41] . We previously found that miR-155 and miR-130a were significantly upregulated in COVID-19 infected patients when compared to non-infected negative controls [7] .…”

Epigenetic modulation of myeloid cell functions in HIV and SARS-CoV-2 infection

“…Has-mirR-208a and has-miR-499 were previously found to be associated with myocardial/cardiomyocyte damage and have been observed in up to 57% of hospitalized COVID-19 patients [ 113 ]. Has-miR-155 has been shown to be a key regulator of innate and adaptive immune response, targeting genes associated with defense against viral infections such as Influenza A virus and SARS-CoV-2 [ 114 , 115 ]. Although COVID-19 and Influenza-ARDS patients, for example, have similar symptoms, the two groups can interestingly be distinguished by differences in the concentrations of has-miR-155 and has-miR-499 [ 112 ].…”

Correlation Study of Peripheral Blood miR-155 and miR-146a Expression Levels with Diabetic Peripheral Neuropathy in Patients with Type 2 Diabetes

“…Increasing evidence suggests their involvement in diabetes and its complications, particularly diabetic neuropathies [6] . miR-155 regulates over 241 genes, playing a role in various physiological and pathological processes, including haematopoietic lineage differentiation, in ammatory responses, immunity, cancer, cardiovascular diseases and notably diabetes [7,8,9] . In T2DM, reduced levels of miR-155 across various mediums, including plasma, peripheral blood cells, platelets and urine, have been consistently observed across different ethnicities [8] .…”