Year: 2021
Type: article
Abstract: COVID-19 is caused by SARS-CoV-2 (SC2) and is more prevalent and severe in elderly and patients with comorbid diseases (CM). Because chitinase 3-like-1 (CHI3L1) is induced during aging and CM, the relationships between CHI3L1 and SC2 were investigated. Here, we demonstrate that CHI3L1 is a potent stimulator of the SC2 receptor angiotensin converting enzyme 2 (ACE2) and viral spike protein priming proteases (SPP), that ACE2 and SPP are induced during aging, and that anti-CHI3L1, kasugamycin, and inhibitors of phosphorylation abrogate these ACE2- and SPP-inductive events. Human studies also demonstrate that the levels of circulating CHI3L1 are increased in the elderly and patients with CM, where they correlate with COVID-19 severity. These studies demonstrate that CHI3L1 is a potent stimulator of ACE2 and SPP, that this induction is a major mechanism contributing to the effects of aging during SC2 infection, and that CHI3L1 co-opts the CHI3L1 axis to augment SC2 infection. CHI3L1 plays a critical role in the pathogenesis of and is an attractive therapeutic target in COVID-19.
Source: JCI Insight
Institutions: Brown University, Lifespan, Yale University, Kurume University
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $4,100
Funders: U.S. Department of Defense, Brown University, Department of Defence, Australian Government, National Institutes of Health, Japan Society for the Promotion of Science, National Institute on Aging, National Heart, Lung, and Blood Institute, National Institute of General Medical Sciences, Medical Research and Materiel Command
Awards: The reduction of NLRX1 and its role in pulmonary aging, G2040153736, YKL-40 in Idiopathic Pulmonary Fibrosis and Kidney Transplantation, Mechanisms of CHI3L1-mediated p53 suppression in the early stage of colon cancer, Ptotective effect of xanthine derivatives on colitis-associated dysplasia, G3842720522, G4119534169, G4817055038, G5407337374, G5514976981, G5850682332, G6441617921, G6933543796, Chitinase1 as a Biomarker and Therapeutic Target in Scleroderma Lung Disease, Stem Cells and Aging, G8687253429, The Reduction of NLRX1 and Its Role in Pulmonary Aging, G9000106687, Distinct and Overlapping Pathways of Fibrosis and Emphysema in Cigarette Smokers
OpenAlex ID: W3213626129