Genome-Wide CRISPR Screens Identify Mucins as Key Host Factors Restricting SARS-CoV-2 Infection

Researchers from the University of California, Berkeley, have conducted a comprehensive study to understand the interactions between the SARS-CoV-2 virus and human host factors. The study, published in Nature Genetics, utilized genome-wide CRISPR knockout and activation screens in human lung epithelial cells to identify host factors that influence viral infection. The research identified mucins as a prominent viral restriction network that inhibits SARS-CoV-2 infection in vitro and in murine models.

Key Takeaways:

• 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 identified mucins as key host factors restricting viral infection.
• Mucins are a family of high molecular weight glycoproteins that inhibit SARS-CoV-2 infection in vitro and in murine models.
• The study further found that mucins also inhibit infection of diverse respiratory viruses, highlighting their role as a host defense mechanism.
• The research provides a physiologically relevant starting point for new host-directed therapeutics and highlights the importance of airway mucins as a key component of the host's immune response to SARS-CoV-2.
• The study was funded by the National Science Foundation (NSF), NIH/National Cancer Institute (NCI) F32 Postdoctoral Fellowship, American Cancer Society, and other organizations.
• The research team included authors from the University of California, Berkeley, as well as other institutions, including the University of North Carolina at Chapel Hill and the North Carolina Coronavirus Relief Fund.

Statistics:

• The study utilized genome-wide CRISPR knockout and activation screens to identify host factors that influence SARS-CoV-2 infection.
• The screens identified 346 protein-coding genes and 225 long non-coding RNAs as proviral host factors.
• Mucins were found to be the most significant host restriction factor, inhibiting SARS-CoV-2 infection in vitro and in murine models.
• The study found that SARS-CoV-2 infection was significantly reduced by 50-70% in the presence of mucins.
• The research highlights the potential of mucins as a therapeutic target for the development of host-directed therapeutics.

Sources:

• Research article: Genome-wide Bidirectional Crispr Screens Identify Mucins As Host Factors Modulating Sars-cov-2 Infection. Nature Genetics, 2022.
• Funding organizations: National Science Foundation (NSF), NIH/National Cancer Institute (NCI) F32 Postdoctoral Fellowship, American Cancer Society, National Science Foundation (NSF), Caring Together Research Fund, United States Department of Defense, NIH National Cancer Institute (NCI), North Carolina Policy Collaboratory at the University of North Carolina at Chapel Hill, North Carolina Coronavirus Relief Fund, National Institute of Diabetes and Digestive and Kidney Diseases and National Heart, Lung, and Blood Institute institutes of the NIH, Italian Cystic Fibrosis Research Foundation, National Institutes of Health (NIH) - USA, NCI Center Core Support Grant, Burroughs Wellcome Fund (Investigators in the Pathogenesis of Infectious Disease), National Institutes of Health (NIH) - USA, NIH National Institute of Allergy & Infectious Diseases (NIAID), Burroughs Wellcome Fund, Ludwig Family Foundation, Mathers Foundation, Fast Grants.
• News source: Genomics & Genetics Weekly.