دورية
Genome-wide bidirectional CRISPR screens identify mucins as host factors modulating SARS-CoV-2 infection
| العنوان: | Genome-wide bidirectional CRISPR screens identify mucins as host factors modulating SARS-CoV-2 infection |
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| المؤلفون: | 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. |
| المصدر: | Nature Genetics; August 2022, Vol. 54 Issue: 8 p1078-1089, 12p |
| مستخلص: | 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 ACE2and 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. |
| قاعدة البيانات: | Supplemental Index |
| تدمد: | 10614036 15461718 |
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| DOI: | 10.1038/s41588-022-01131-x |