Type I and Type III Interferons Restrict SARS-CoV-2 Infection of Human Airway Epithelial Cultures

Author:

Vanderheiden Abigail12345,Ralfs Philipp456,Chirkova Tatiana1234,Upadhyay Amit A.457,Zimmerman Matthew G.12345,Bedoya Shamika68,Aoued Hadj457,Tharp Gregory M.457,Pellegrini Kathryn L.457,Manfredi Candela9,Sorscher Eric9,Mainou Bernardo123ORCID,Lobby Jenna L.6,Kohlmeier Jacob E.68,Lowen Anice C.68ORCID,Shi Pei-Yong10,Menachery Vineet D.11ORCID,Anderson Larry J.1234,Grakoui Arash12346,Bosinger Steven E.457,Suthar Mehul S.12345ORCID

Affiliation:

1. Center for Childhood Infections and Vaccines (CCIV), Atlanta, Georgia, USA

2. Children’s Healthcare of Atlanta, Atlanta, Georgia, USA

3. Department of Pediatrics, Division of Infectious Disease, Emory University School of Medicine, Atlanta, Georgia, USA

4. Emory Vaccine Center, Emory University School of Medicine, Atlanta, Georgia, USA

5. Yerkes National Primate Research Center, Atlanta, Georgia, USA

6. Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia, USA

7. Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, USA

8. Emory-UGA Center of Excellence of Influenza Research and Surveillance (CEIRS), Atlanta Georgia, USA

9. Department of Pediatrics, Division of Pulmonary Medicine, Emory University School of Medicine, Atlanta, Georgia, USA

10. Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch, Galveston, Texas, USA

11. Department of Microbiology and Immunology, Institute for Human Infection and Immunity, World Reference Center for Emerging Viruses and Arboviruses, University of Texas Medical Branch, Galveston, Texas, USA

Abstract

The current pandemic of respiratory illness, COVID-19, is caused by a recently emerged coronavirus named SARS-CoV-2. This virus infects airway and lung cells causing fever, dry cough, and shortness of breath. Severe cases of COVID-19 can result in lung damage, low blood oxygen levels, and even death. As there are currently no vaccines approved for use in humans, studies of the mechanisms of SARS-CoV-2 infection are urgently needed. Our research identifies an excellent system to model SARS-CoV-2 infection of the human airways that can be used to test various treatments. Analysis of infection in this model system found that human airway epithelial cell cultures induce a strong proinflammatory cytokine response yet block the production of type I and III IFNs to SARS-CoV-2. However, treatment of airway cultures with the immune molecules type I or type III interferon (IFN) was able to inhibit SARS-CoV-2 infection. Thus, our model system identified type I or type III IFN as potential antiviral treatments for COVID-19 patients.

Funder

Center for Childhood Infections and Vaccines

Centers of Excellence for Influenza Research and Surveillance

HHS | National Institutes of Health

Emory University

Children's Healthcare of Atlanta

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

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