-transparent.png){kind=logo}
Genome-wide bidirectional CRISPR screens identify mucins as host factors modulating SARS-CoV-2 infection. 2022
Scott B Biering, and
Sylvia A Sarnik, and
Eleanor Wang, and
James R Zengel, and
Sarah R Leist, and
Alexandra Schäfer, and
Varun Sathyan, and
Padraig Hawkins, and
Kenichi Okuda, and
Cyrus Tau, and
Aditya R Jangid, and
Connor V Duffy, and
Jin Wei, and
Rodney C Gilmore, and
Mia Madel Alfajaro, and
Madison S Strine, and
Xammy Nguyenla, and
Erik Van Dis, and
Carmelle Catamura, and
Livia H Yamashiro, and
Julia A Belk, and
Adam Begeman, and
Jessica C Stark, and
D Judy Shon, and
Douglas M Fox, and
Shahrzad Ezzatpour, and
Emily Huang, and
Nico Olegario, and
Arjun Rustagi, and
Allison S Volmer, and
Alessandra Livraghi-Butrico, and
Eddie Wehri, and
Richard R Behringer, and
Dong-Joo Cheon, and
Julia Schaletzky, and
Hector C Aguilar, and
Andreas S Puschnik, and
Brian Button, and
Benjamin A Pinsky, and
Catherine A Blish, and
Ralph S Baric, and
Wanda K O'Neal, and
Carolyn R Bertozzi, and
Craig B Wilen, and
Richard C Boucher, and
Jan E Carette, and
Sarah A Stanley, and
Eva Harris, and
Silvana Konermann, and
Patrick D Hsu
Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA, USA.
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.
Related Publications
Scott B Biering, and
Sylvia A Sarnik, and
Eleanor Wang, and
James R Zengel, and
Sarah R Leist, and
Alexandra Schäfer, and
Varun Sathyan, and
Padraig Hawkins, and
Kenichi Okuda, and
Cyrus Tau, and
Aditya R Jangid, and
Connor V Duffy, and
Jin Wei, and
Rodney C Gilmore, and
Mia Madel Alfajaro, and
Madison S Strine, and
Xammy Nguyenla, and
Erik Van Dis, and
Carmelle Catamura, and
Livia H Yamashiro, and
Julia A Belk, and
Adam Begeman, and
Jessica C Stark, and
D Judy Shon, and
Douglas M Fox, and
Shahrzad Ezzatpour, and
Emily Huang, and
Nico Olegario, and
Arjun Rustagi, and
Allison S Volmer, and
Alessandra Livraghi-Butrico, and
Eddie Wehri, and
Richard R Behringer, and
Dong-Joo Cheon, and
Julia Schaletzky, and
Hector C Aguilar, and
Andreas S Puschnik, and
Brian Button, and
Benjamin A Pinsky, and
Catherine A Blish, and
Ralph S Baric, and
Wanda K O'Neal, and
Carolyn R Bertozzi, and
Craig B Wilen, and
Richard C Boucher, and
Jan E Carette, and
Sarah A Stanley, and
Eva Harris, and
Silvana Konermann, and
Patrick D Hsu
January 2021,
Cell,
Scott B Biering, and
Sylvia A Sarnik, and
Eleanor Wang, and
James R Zengel, and
Sarah R Leist, and
Alexandra Schäfer, and
Varun Sathyan, and
Padraig Hawkins, and
Kenichi Okuda, and
Cyrus Tau, and
Aditya R Jangid, and
Connor V Duffy, and
Jin Wei, and
Rodney C Gilmore, and
Mia Madel Alfajaro, and
Madison S Strine, and
Xammy Nguyenla, and
Erik Van Dis, and
Carmelle Catamura, and
Livia H Yamashiro, and
Julia A Belk, and
Adam Begeman, and
Jessica C Stark, and
D Judy Shon, and
Douglas M Fox, and
Shahrzad Ezzatpour, and
Emily Huang, and
Nico Olegario, and
Arjun Rustagi, and
Allison S Volmer, and
Alessandra Livraghi-Butrico, and
Eddie Wehri, and
Richard R Behringer, and
Dong-Joo Cheon, and
Julia Schaletzky, and
Hector C Aguilar, and
Andreas S Puschnik, and
Brian Button, and
Benjamin A Pinsky, and
Catherine A Blish, and
Ralph S Baric, and
Wanda K O'Neal, and
Carolyn R Bertozzi, and
Craig B Wilen, and
Richard C Boucher, and
Jan E Carette, and
Sarah A Stanley, and
Eva Harris, and
Silvana Konermann, and
Patrick D Hsu
August 2022,
Nature genetics,
Scott B Biering, and
Sylvia A Sarnik, and
Eleanor Wang, and
James R Zengel, and
Sarah R Leist, and
Alexandra Schäfer, and
Varun Sathyan, and
Padraig Hawkins, and
Kenichi Okuda, and
Cyrus Tau, and
Aditya R Jangid, and
Connor V Duffy, and
Jin Wei, and
Rodney C Gilmore, and
Mia Madel Alfajaro, and
Madison S Strine, and
Xammy Nguyenla, and
Erik Van Dis, and
Carmelle Catamura, and
Livia H Yamashiro, and
Julia A Belk, and
Adam Begeman, and
Jessica C Stark, and
D Judy Shon, and
Douglas M Fox, and
Shahrzad Ezzatpour, and
Emily Huang, and
Nico Olegario, and
Arjun Rustagi, and
Allison S Volmer, and
Alessandra Livraghi-Butrico, and
Eddie Wehri, and
Richard R Behringer, and
Dong-Joo Cheon, and
Julia Schaletzky, and
Hector C Aguilar, and
Andreas S Puschnik, and
Brian Button, and
Benjamin A Pinsky, and
Catherine A Blish, and
Ralph S Baric, and
Wanda K O'Neal, and
Carolyn R Bertozzi, and
Craig B Wilen, and
Richard C Boucher, and
Jan E Carette, and
Sarah A Stanley, and
Eva Harris, and
Silvana Konermann, and
Patrick D Hsu
May 2021,
bioRxiv : the preprint server for biology,
Scott B Biering, and
Sylvia A Sarnik, and
Eleanor Wang, and
James R Zengel, and
Sarah R Leist, and
Alexandra Schäfer, and
Varun Sathyan, and
Padraig Hawkins, and
Kenichi Okuda, and
Cyrus Tau, and
Aditya R Jangid, and
Connor V Duffy, and
Jin Wei, and
Rodney C Gilmore, and
Mia Madel Alfajaro, and
Madison S Strine, and
Xammy Nguyenla, and
Erik Van Dis, and
Carmelle Catamura, and
Livia H Yamashiro, and
Julia A Belk, and
Adam Begeman, and
Jessica C Stark, and
D Judy Shon, and
Douglas M Fox, and
Shahrzad Ezzatpour, and
Emily Huang, and
Nico Olegario, and
Arjun Rustagi, and
Allison S Volmer, and
Alessandra Livraghi-Butrico, and
Eddie Wehri, and
Richard R Behringer, and
Dong-Joo Cheon, and
Julia Schaletzky, and
Hector C Aguilar, and
Andreas S Puschnik, and
Brian Button, and
Benjamin A Pinsky, and
Catherine A Blish, and
Ralph S Baric, and
Wanda K O'Neal, and
Carolyn R Bertozzi, and
Craig B Wilen, and
Richard C Boucher, and
Jan E Carette, and
Sarah A Stanley, and
Eva Harris, and
Silvana Konermann, and
Patrick D Hsu
May 2021,
Research square,
Scott B Biering, and
Sylvia A Sarnik, and
Eleanor Wang, and
James R Zengel, and
Sarah R Leist, and
Alexandra Schäfer, and
Varun Sathyan, and
Padraig Hawkins, and
Kenichi Okuda, and
Cyrus Tau, and
Aditya R Jangid, and
Connor V Duffy, and
Jin Wei, and
Rodney C Gilmore, and
Mia Madel Alfajaro, and
Madison S Strine, and
Xammy Nguyenla, and
Erik Van Dis, and
Carmelle Catamura, and
Livia H Yamashiro, and
Julia A Belk, and
Adam Begeman, and
Jessica C Stark, and
D Judy Shon, and
Douglas M Fox, and
Shahrzad Ezzatpour, and
Emily Huang, and
Nico Olegario, and
Arjun Rustagi, and
Allison S Volmer, and
Alessandra Livraghi-Butrico, and
Eddie Wehri, and
Richard R Behringer, and
Dong-Joo Cheon, and
Julia Schaletzky, and
Hector C Aguilar, and
Andreas S Puschnik, and
Brian Button, and
Benjamin A Pinsky, and
Catherine A Blish, and
Ralph S Baric, and
Wanda K O'Neal, and
Carolyn R Bertozzi, and
Craig B Wilen, and
Richard C Boucher, and
Jan E Carette, and
Sarah A Stanley, and
Eva Harris, and
Silvana Konermann, and
Patrick D Hsu
April 2022,
Nature communications,
Scott B Biering, and
Sylvia A Sarnik, and
Eleanor Wang, and
James R Zengel, and
Sarah R Leist, and
Alexandra Schäfer, and
Varun Sathyan, and
Padraig Hawkins, and
Kenichi Okuda, and
Cyrus Tau, and
Aditya R Jangid, and
Connor V Duffy, and
Jin Wei, and
Rodney C Gilmore, and
Mia Madel Alfajaro, and
Madison S Strine, and
Xammy Nguyenla, and
Erik Van Dis, and
Carmelle Catamura, and
Livia H Yamashiro, and
Julia A Belk, and
Adam Begeman, and
Jessica C Stark, and
D Judy Shon, and
Douglas M Fox, and
Shahrzad Ezzatpour, and
Emily Huang, and
Nico Olegario, and
Arjun Rustagi, and
Allison S Volmer, and
Alessandra Livraghi-Butrico, and
Eddie Wehri, and
Richard R Behringer, and
Dong-Joo Cheon, and
Julia Schaletzky, and
Hector C Aguilar, and
Andreas S Puschnik, and
Brian Button, and
Benjamin A Pinsky, and
Catherine A Blish, and
Ralph S Baric, and
Wanda K O'Neal, and
Carolyn R Bertozzi, and
Craig B Wilen, and
Richard C Boucher, and
Jan E Carette, and
Sarah A Stanley, and
Eva Harris, and
Silvana Konermann, and
Patrick D Hsu
June 2020,
bioRxiv : the preprint server for biology,
Scott B Biering, and
Sylvia A Sarnik, and
Eleanor Wang, and
James R Zengel, and
Sarah R Leist, and
Alexandra Schäfer, and
Varun Sathyan, and
Padraig Hawkins, and
Kenichi Okuda, and
Cyrus Tau, and
Aditya R Jangid, and
Connor V Duffy, and
Jin Wei, and
Rodney C Gilmore, and
Mia Madel Alfajaro, and
Madison S Strine, and
Xammy Nguyenla, and
Erik Van Dis, and
Carmelle Catamura, and
Livia H Yamashiro, and
Julia A Belk, and
Adam Begeman, and
Jessica C Stark, and
D Judy Shon, and
Douglas M Fox, and
Shahrzad Ezzatpour, and
Emily Huang, and
Nico Olegario, and
Arjun Rustagi, and
Allison S Volmer, and
Alessandra Livraghi-Butrico, and
Eddie Wehri, and
Richard R Behringer, and
Dong-Joo Cheon, and
Julia Schaletzky, and
Hector C Aguilar, and
Andreas S Puschnik, and
Brian Button, and
Benjamin A Pinsky, and
Catherine A Blish, and
Ralph S Baric, and
Wanda K O'Neal, and
Carolyn R Bertozzi, and
Craig B Wilen, and
Richard C Boucher, and
Jan E Carette, and
Sarah A Stanley, and
Eva Harris, and
Silvana Konermann, and
Patrick D Hsu
January 2022,
Genome medicine,
Scott B Biering, and
Sylvia A Sarnik, and
Eleanor Wang, and
James R Zengel, and
Sarah R Leist, and
Alexandra Schäfer, and
Varun Sathyan, and
Padraig Hawkins, and
Kenichi Okuda, and
Cyrus Tau, and
Aditya R Jangid, and
Connor V Duffy, and
Jin Wei, and
Rodney C Gilmore, and
Mia Madel Alfajaro, and
Madison S Strine, and
Xammy Nguyenla, and
Erik Van Dis, and
Carmelle Catamura, and
Livia H Yamashiro, and
Julia A Belk, and
Adam Begeman, and
Jessica C Stark, and
D Judy Shon, and
Douglas M Fox, and
Shahrzad Ezzatpour, and
Emily Huang, and
Nico Olegario, and
Arjun Rustagi, and
Allison S Volmer, and
Alessandra Livraghi-Butrico, and
Eddie Wehri, and
Richard R Behringer, and
Dong-Joo Cheon, and
Julia Schaletzky, and
Hector C Aguilar, and
Andreas S Puschnik, and
Brian Button, and
Benjamin A Pinsky, and
Catherine A Blish, and
Ralph S Baric, and
Wanda K O'Neal, and
Carolyn R Bertozzi, and
Craig B Wilen, and
Richard C Boucher, and
Jan E Carette, and
Sarah A Stanley, and
Eva Harris, and
Silvana Konermann, and
Patrick D Hsu
August 2023,
Cell reports,
Scott B Biering, and
Sylvia A Sarnik, and
Eleanor Wang, and
James R Zengel, and
Sarah R Leist, and
Alexandra Schäfer, and
Varun Sathyan, and
Padraig Hawkins, and
Kenichi Okuda, and
Cyrus Tau, and
Aditya R Jangid, and
Connor V Duffy, and
Jin Wei, and
Rodney C Gilmore, and
Mia Madel Alfajaro, and
Madison S Strine, and
Xammy Nguyenla, and
Erik Van Dis, and
Carmelle Catamura, and
Livia H Yamashiro, and
Julia A Belk, and
Adam Begeman, and
Jessica C Stark, and
D Judy Shon, and
Douglas M Fox, and
Shahrzad Ezzatpour, and
Emily Huang, and
Nico Olegario, and
Arjun Rustagi, and
Allison S Volmer, and
Alessandra Livraghi-Butrico, and
Eddie Wehri, and
Richard R Behringer, and
Dong-Joo Cheon, and
Julia Schaletzky, and
Hector C Aguilar, and
Andreas S Puschnik, and
Brian Button, and
Benjamin A Pinsky, and
Catherine A Blish, and
Ralph S Baric, and
Wanda K O'Neal, and
Carolyn R Bertozzi, and
Craig B Wilen, and
Richard C Boucher, and
Jan E Carette, and
Sarah A Stanley, and
Eva Harris, and
Silvana Konermann, and
Patrick D Hsu
February 2021,
Nature communications,
Scott B Biering, and
Sylvia A Sarnik, and
Eleanor Wang, and
James R Zengel, and
Sarah R Leist, and
Alexandra Schäfer, and
Varun Sathyan, and
Padraig Hawkins, and
Kenichi Okuda, and
Cyrus Tau, and
Aditya R Jangid, and
Connor V Duffy, and
Jin Wei, and
Rodney C Gilmore, and
Mia Madel Alfajaro, and
Madison S Strine, and
Xammy Nguyenla, and
Erik Van Dis, and
Carmelle Catamura, and
Livia H Yamashiro, and
Julia A Belk, and
Adam Begeman, and
Jessica C Stark, and
D Judy Shon, and
Douglas M Fox, and
Shahrzad Ezzatpour, and
Emily Huang, and
Nico Olegario, and
Arjun Rustagi, and
Allison S Volmer, and
Alessandra Livraghi-Butrico, and
Eddie Wehri, and
Richard R Behringer, and
Dong-Joo Cheon, and
Julia Schaletzky, and
Hector C Aguilar, and
Andreas S Puschnik, and
Brian Button, and
Benjamin A Pinsky, and
Catherine A Blish, and
Ralph S Baric, and
Wanda K O'Neal, and
Carolyn R Bertozzi, and
Craig B Wilen, and
Richard C Boucher, and
Jan E Carette, and
Sarah A Stanley, and
Eva Harris, and
Silvana Konermann, and
Patrick D Hsu
November 2018,
PLoS genetics,
