Mice lacking the adaptor protein that initiates an antiviral response downstream of the RNA helicases retinoic acid–inducible gene I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5) have recently been described. These studies highlight the essential and nonredundant role of nucleic acid recognition in the induction of type I interferon production and raise important questions regarding the nature of cell-autonomous virus detection in coordinating the antiviral response.

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