Activation of stress response during viral infection:
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Virus infection leads to activation of the interferon-induced endoribonuclease, RNase L, which results in the degradation of viral and cellular RNAs. Both cellular and viral RNA cleavage products of RNase L bind pattern recognition receptors (PRR) like Retinoic acid-inducible I (Rig-I) and or melanoma differentiation-associated protein 5 (MDA5) to further amplify interferon (IFN) production and antiviral response. Although much is known about the mechanics of ligand binding and PRR activation, how the cells coordinate RNA sensing to signaling response and interferon production remains unclear. We show that RNA cleavage products of RNase L activity induce the formation of antiviral stress granule (avSG) by regulating the activation of double-stranded RNA (dsRNA)-dependent protein kinase R (PKR) and recruit antiviral proteins Rig-I, PKR, OAS, and RNase L to avSG. SG formed during viral infection, antiviral stress granules (avSG), are distinct from canonical SG in that they recruit antiviral proteins and components of signaling pathways to function as a platform to mount an effective antiviral response. Our studies will address how the stress-specific differences in SG composition, assembly, and dynamics impact the outcome of diverse viral infections.