American Society for Microbiology, Journal of Virology, 23(92), 2018
DOI: 10.1128/jvi.01368-18
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Human noroviruses are a leading cause of gastroenteritis throughout the world but are challenging to study in vivo and in vitro . Murine norovirus (MNoV) provides a tractable genetic and small-animal model to study norovirus biology and immune responses. Interferons are critical mediators of antiviral immunity, but excessive expression can dysregulate the immune system. IFN-λ plays an important role at mucosal surfaces, including the gastrointestinal tract, and both IFN-λ and commensal enteric bacteria are important modulators of persistent MNoV infection. LUBAC, of which HOIL1 is a component, is reported to inhibit type I IFN induction after RIG-I stimulation. We show, in contrast, that HOIL1 is critical for type I and III IFN induction during infection with MNoV, a virus that preferentially activates MDA5. Moreover, HOIL1 regulates MNoV infection in vivo . These data reveal distinct functions for LUBAC in these closely related signaling pathways and in modulation of IFN expression.