Details

Autor(en) / Beteiligte

• Biering, Scott B.
• Sarnik, Sylvia A.
• Wang, Eleanor
• Zengel, James R.
• Leist, Sarah R.
• Schäfer, Alexandra
• Sathyan, Varun
• Hawkins, Padraig
• Okuda, Kenichi
• Tau, Cyrus
• Jangid, Aditya R.
• Duffy, Connor V.
• Wei, Jin
• Gilmore, Rodney C.
• Alfajaro, Mia Madel
• Strine, Madison S.
• Nguyenla, Xammy
• Van Dis, Erik
• Catamura, Carmelle
• Yamashiro, Livia H.
• Belk, Julia A.
• Begeman, Adam
• Stark, Jessica C.
• Shon, D. Judy
• Fox, Douglas M.
• Ezzatpour, Shahrzad
• Huang, Emily
• Olegario, Nico
• Rustagi, Arjun
• Volmer, Allison S.
• Livraghi-Butrico, Alessandra
• Wehri, Eddie
• Behringer, Richard R.
• Cheon, Dong-Joo
• Schaletzky, Julia
• Aguilar, Hector C.
• Puschnik, Andreas S.
• Button, Brian
• Pinsky, Benjamin A.
• Blish, Catherine A.
• Baric, Ralph S.
• O’Neal, Wanda K.
• Bertozzi, Carolyn R.
• Wilen, Craig B.
• Boucher, Richard C.
• Carette, Jan E.
• Stanley, Sarah A.
• Harris, Eva
• Konermann, Silvana
• Hsu, Patrick D.

Titel

Genome-wide bidirectional CRISPR screens identify mucins as host factors modulating SARS-CoV-2 infection

Ist Teil von

• Nature genetics, 2022-08, Vol.54 (8), p.1078-1089

Ort / Verlag

New York: Nature Publishing Group

Erscheinungsjahr

2022

Link zum Volltext

Beschreibungen/Notizen

• 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.