ADAM9 promotes type I interferon-mediated innate immunity during encephalomyocarditis virus infection.
Nat Commun
; 15(1): 4153, 2024 May 16.
Article
em En
| MEDLINE
| ID: mdl-38755212
ABSTRACT
Viral myocarditis, an inflammatory disease of the heart, causes significant morbidity and mortality. Type I interferon (IFN)-mediated antiviral responses protect against myocarditis, but the mechanisms are poorly understood. We previously identified A Disintegrin And Metalloproteinase domain 9 (ADAM9) as an important factor in viral pathogenesis. ADAM9 is implicated in a range of human diseases, including inflammatory diseases; however, its role in viral infection is unknown. Here, we demonstrate that mice lacking ADAM9 are more susceptible to encephalomyocarditis virus (EMCV)-induced death and fail to mount a characteristic type I IFN response. This defect in type I IFN induction is specific to positive-sense, single-stranded RNA (+ ssRNA) viruses and involves melanoma differentiation-associated protein 5 (MDA5)-a key receptor for +ssRNA viruses. Mechanistically, ADAM9 binds to MDA5 and promotes its oligomerization and thereby downstream mitochondrial antiviral-signaling protein (MAVS) activation in response to EMCV RNA stimulation. Our findings identify a role for ADAM9 in the innate antiviral response, specifically MDA5-mediated IFN production, which protects against virus-induced cardiac damage, and provide a potential therapeutic target for treatment of viral myocarditis.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Interferon Tipo I
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Infecções por Cardiovirus
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Vírus da Encefalomiocardite
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Proteínas ADAM
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Helicase IFIH1 Induzida por Interferon
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Imunidade Inata
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Proteínas de Membrana
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Miocardite
Limite:
Animals
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article