ena-STUDY-MAASTRICHT UNIVERSITY-02-01-2021-04:57:02:300-258
An Inflamed and Oxidized Environment promotes SARS-CoV-2 to dock Endothelial Cells and Cardiomyocytes using Extracellular Vesicles, Exosomes, and Neuropilin-1 in Human Heart Failure Patients
The SARS-CoV-2 virus currently driving the COVID-19 pandemic can trigger severe acute respiratory syndrome, an illness that may be particularly serious and in some cases even fatal amongst those with pre-existing heart conditions. In this study, we investigated 1) whether SARS-CoV-2 is found in the heart, 2) the mechanisms of virus entry into the heart, and 3) the consequences of viral entry into cardiac cells. We found that extracellular vesicles, exosomes and NRP-1 significantly potentiate SARS-CoV-2 infectivity and entry, which is further promoted by an inflamed and oxidized cellular environment. We also defined the receptor-mediated signalling events responsible for IL6-driven neutrophil trafficking. This results in increased protease activity leads to cell damage and apoptosis. Our data provide new insights into the mechanisms of SARS-CoV-2 entry into the heart and define promising targets of antiviral interventions for COVID-19 patients suffering from heart failure and co-morbidities.
The SARS-CoV-2 virus currently driving the COVID-19 pandemic can trigger severe acute respiratory syndrome, an illness that may be particularly serious and in some cases even fatal amongst those with pre-existing heart conditions. In this study, we investigated 1) whether SARS-CoV-2 is found in the heart, 2) the mechanisms of virus entry into the heart, and 3) the consequences of viral entry into cardiac cells. We found that extracellular vesicles, exosomes and NRP-1 significantly potentiate SARS-CoV-2 infectivity and entry, which is further promoted by an inflamed and oxidized cellular environment. We also defined the receptor-mediated signalling events responsible for IL6-driven neutrophil trafficking. This results in increased protease activity leads to cell damage and apoptosis. Our data provide new insights into the mechanisms of SARS-CoV-2 entry into the heart and define promising targets of antiviral interventions for COVID-19 patients suffering from heart failure and co-morbidities.