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

• DOI: 10.1128/mbio.02734-18
• Publication Date: 2019-02-04T12:11:21Z
• Authors: Lindsey E. Bazzone; Michael King; Christopher R. Ma...; Pyae P. Kyawe; Paul Meraner; Daniel Lindstrom; Joselyn Rojas-Qui...; Caroline A. Owen; Jennifer P. Wang; Abraham L. Brass; Evelyn A. Kurt-Jones; Robert W. Finberg
• Keywords: 570; 572; 60405 Gene Expression (incl. Microarray and other genome-wide approaches); Immunology; FOS: Health sciences; Models, Biological; Microbiology; functional genomic screen; Cell Line; Gene Knockout Techniques; Mice; 03 medical and health sciences; Virology; Enzymes and Coenzymes; Cardiovirus Infections; Animals; Humans; 110707 Innate Immunity; Genetic Testing; Amino Acids; Encephalomyocarditis virus; 110804 Medical Virology; Immunology and Infectious Disease; Disease Resistance; Mice, Knockout; 0303 health sciences; 60502 Infectious Agents; a disintegrin and metalloproteinase 9 domain (ADAM9); 110704 Cellular Immunology; FOS: Clinical medicine; and Proteins; Membrane Proteins; encephalomyocarditis virus; QR1-502; 3. Good health; ADAM Proteins; Virus Diseases; FOS: Biological sciences; Viruses; 60307 Host-Parasite Interactions; Peptides; Research Article

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.