ADAM9 promotes type I interferon-mediated innate immunity during encephalomyocarditis virus infection.

Autor: Bazzone, Lindsey E., Zhu, Junji, King, Michael, Liu, GuanQun, Guo, Zhiru, MacKay, Christopher R., Kyawe, Pyae P., Qaisar, Natasha, Rojas-Quintero, Joselyn, Owen, Caroline A., Brass, Abraham L., McDougall, William, Baer, Christina E., Cashman, Timothy, Trivedi, Chinmay M., Gack, Michaela U., Finberg, Robert W., Kurt-Jones, Evelyn A.
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Zdroj: Nature Communications; 5/16/2024, Vol. 15 Issue 1, p1-14, 14p
Abstrakt: 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. Mice lacking A Disintegrin and Metalloproteinase 9 (ADAM9) do not mount Type 1 interferon responses against encephalomyocarditis infection. Here, Bazzone et al show that ADAM9 regulates innate immune responses via by MDA5. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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