Faculty, Staff and Student Publications
Publication Date
8-1-2022
Journal
Nature Genetics
DOI
10.1038/s41588-022-01131-x
PMID
35879412
PMCID
PMC9355872
PubMedCentral® Posted Date
July 2022
PubMedCentral® Full Text Version
Post-print
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
Published Open-Access
yes
Recommended Citation
Biering, Scott B; Sarnik, Sylvia A; Wang, Eleanor; et al., "Genome-Wide Bidirectional Crispr Screens Identify Mucins as Host Factors Modulating SARS-CoV-2 Infection" (2022). Faculty, Staff and Student Publications. 260.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/260
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