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.
【초록키워드】 COVID-19, coronavirus disease, severe acute respiratory syndrome coronavirus 2, SARS-CoV-2, viral infection, Coronavirus disease 2019, ACE2, TMPRSS2, coronavirus, acute respiratory distress syndrome, Antiviral, SARS-COV-2 infection, Infection, Respiratory illness, Symptom, progression, in vitro, severe acute respiratory syndrome Coronavirus, airway, respiratory viruses, CRISPR, family, Viral, human lung, epithelial cells, mucin, respiratory, mucins, expression, Epigenetic, Critical, mechanism, acute respiratory distress, host defense, Pathways, epithelial cell, respiratory distress, starting point, Transport, acute respiratory syndrome, Activation, Factor, Regulation, defense mechanism, acute respiratory syndrome coronavirus, infected individuals, syndrome, murine models, Highlights, human lung epithelial cells, Defense, SARS-CoV-2 entry factors, clathrin, Host, molecular weight, SARS-CoV-2-host interactions, highlight, transcriptional, inflammatory signaling, inhibit, conducted, functional, provide, cause, mild respiratory, SARS-CoV-2-host interaction, the SARS-CoV-2, 【제목키워드】 CRISPR screen, bidirectional, mucin, Factor, Host, identify, modulating,