Faculty, Staff and Student Publications
Publication Date
8-1-2022
Journal
Nature Genetics
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a range of symptoms in infected individuals, from mild respiratory illness to acute respiratory distress syndrome. A systematic understanding of host factors influencing viral infection is critical to elucidate SARS-CoV-2-host interactions and the progression of Coronavirus disease 2019 (COVID-19). Here, we conducted genome-wide CRISPR knockout and activation screens in human lung epithelial cells with endogenous expression of the SARS-CoV-2 entry factors ACE2 and TMPRSS2. We uncovered proviral and antiviral factors across highly interconnected host pathways, including clathrin transport, inflammatory signaling, cell-cycle regulation, and transcriptional and epigenetic regulation. We further identified mucins, a family of high molecular weight glycoproteins, as a prominent viral restriction network that inhibits SARS-CoV-2 infection in vitro and in murine models. These mucins also inhibit infection of diverse respiratory viruses. This functional landscape of SARS-CoV-2 host factors provides a physiologically relevant starting point for new host-directed therapeutics and highlights airway mucins as a host defense mechanism.
Keywords
Animals, COVID-19, Clustered Regularly Interspaced Short Palindromic Repeats, Epigenesis, Genetic, Humans, Mice, Mucins, SARS-CoV-2
Included in
Bioinformatics Commons, Biomedical Informatics Commons, Genetics Commons, Medical Sciences Commons, Oncology Commons
Comments
Supplementary Materials
PMID: 35879412