A Disintegrin and Metalloproteinase 9 Domain (ADAM9) Is a Major Susceptibility Factor in the Early Stages of Encephalomyocarditis Virus Infection

Author:

Bazzone Lindsey E.1,King Michael1,MacKay Christopher R.1,Kyawe Pyae P.1,Meraner Paul2,Lindstrom Daniel1,Rojas-Quintero Joselyn3,Owen Caroline A.3,Wang Jennifer P.14,Brass Abraham L.56,Kurt-Jones Evelyn A.14,Finberg Robert W.14

Affiliation:

1. Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA

2. Department of Microbiology and Physiological Systems (MaPS), University of Massachusetts Medical School, Worcester, Massachusetts, USA

3. Division of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USA

4. Program in Innate Immunity, University of Massachusetts Medical School, Worcester, Massachusetts, USA

5. Department of Medicine, Division of Gastroenterology, University of Massachusetts Medical School, Worcester, Massachusetts, USA

6. Peak Gastroenterology Associates, Colorado Springs, Colorado, USA

Abstract

Viral myocarditis is a leading cause of death in the United States, contributing to numerous unexplained deaths in people ≤35 years old. Enteroviruses contribute to many cases of human myocarditis. Encephalomyocarditis virus (EMCV) infection causes viral myocarditis in rodent models, but its receptor requirements have not been fully identified. CRISPR-Cas9 screens can identify host dependency factors essential for EMCV infection and enhance our understanding of key events that follow viral infection, potentially leading to new strategies for preventing viral myocarditis. Using a CRISPR-Cas9 screen, we identified a d isintegrin a nd m etalloproteinase 9 domain (ADAM9) as a major factor required for the early stages of EMCV infection in both human and murine infection.

Funder

American Heart Association and Myocarditis Foundation

Flight Attendants Medical Research Institute Grant

The Brigham and Women's Hospital-Lovelace Respiratory Research Institute Consortium

Department of Defense Congressionally Directed Medical Research Programs

HHS | NIH | National Institute of Allergy and Infectious Diseases

Burroughs Wellcome Fund

Gilead Sciences

Bill and Melinda Gates Foundation

Publisher

American Society for Microbiology

Subject

Virology,Microbiology

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