In the cytoplasm, RIG-I and MDA5 form filaments along the length of dsRNA to activate MAVS, whose aggregation functions as a platform to recruit TRAF proteins for IFN-I and NF-κB signaling activation. dsRNAs are also recognized by PKR to trigger global translation repression and by OAS for RNA degradation and translation shutdown. OAS–RNase L reprograms cellular translation to allow defense mRNAs, such as IFNβ mRNAs, to translate normally. In the endosome, dsRNAs are recognized by TLR3, and such binding activates the downstream adaptor TRIF. ssRNAs in the endosome bind to TLR7 or TLR8, activating MyD88, which further recruits IRAKs to form the Myddosome. Activated TRIF or Myddosome then recruits TRAFs for downstream activation. Red-colored strands represent RNA molecules, and green strands represent DNA molecules. “p” denotes phosphorylation.