Poly(I:C)-injected hM-R822Q Tg mice also developed lethal hypercytokinemia marked by massive IL-6 levels in the serum. Although administration of the viral dsRNA mimic polyinosinic-polycytidylic acid did not have remarkable effects on the cardiac phenotype, dramatic inflammation was observed in the intestines where IFN production was most elevated. hM-R822Q transgenic (Tg) mice developed SMS-like heart fibrosis, aortic valve enlargement, and aortic calcification with a systemic IFN-stimulated gene signature resulting in the activation of the adaptive immune response. With this aim, we generated mice with human MDA5 bearing the SMS-associated mutation R822Q (hM-R822Q).

However, much remains unclear regarding the mechanism of disease progression and how external factors such as infection or immune stimulation with vaccination can affect the immune response.

Gain-of-function mutations in the viral dsRNA sensor melanoma differentiation–associated protein 5 (MDA5) lead to autoimmune IFNopathies, including Singleton–Merten syndrome (SMS) and Aicardi–Goutières syndrome.

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