Genomewide CRISPR knockout screen identified PLAC8 as an essential factor for SADS-CoVs infection

Author:

Tse Longping V.1ORCID,Meganck Rita M.1ORCID,Araba Kenza C.2,Yount Boyd L.1,Shaffer Kendall M.2ORCID,Hou Yixuan J.1ORCID,Munt Jennifer E.1,Adams Lily E.13,Wykoff Jason A.2,Morowitz Jeremy M.4,Dong Stephanie1,Magness Scott T.456,Marzluff William F.7ORCID,Gonzalez Liara M.8,Ehre Camille29,Baric Ralph S.13ORCID

Affiliation:

1. Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514

2. Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514

3. Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514

4. Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514

5. Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514

6. Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill/North Carolina State University, Chapel Hill, NC 27514

7. Integrated Program for Biological and Genome Sciences, Department of Biochemistry & Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514

8. Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606

9. Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514

Abstract

Significance A potential outbreak of swine acute diarrhea syndrome coronavirus (SADS-CoV) in the human population could be devastating. Using genomewide CRISPR knockout screening, we identified the placenta-associated 8 protein (PLAC8) as an essential host factor for SADS-CoV infection, uncovering a novel antiviral target for CoV infection. The PLAC8-related pathway may also have implications for other CoV infections. Given the ability of SADS-CoV to infect human primary cultures without adaptation, our findings lay the foundation for pandemic preparedness for the potential emergence of SADS-CoVs in response to the One Health Initiative.

Funder

HHS | NIH | National Institute of Allergy and Infectious Diseases

HHS | NIH | NIH Office of the Director

HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases

Publisher

Proceedings of the National Academy of Sciences

Subject

Multidisciplinary

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