SARS-CoV INNATE RESPONSE TO dsRNA

Double-stranded RNA (dsRNA) is generated during replication of positive -strand RNA and DNA viruses. The innate immune response pathway is activated in response to HCoV infection by dsRNA-sensing molecules that reside in the cytoplasm of host cells. Once these sensors are activated, they interact with the mitochondrial membrane protein MAVS (mitochondrial antiviral) which in turn stimulates the activation of the TBK1 and IKKɛ kinases. Once activated, these kinases upregulate the activity of crucial transcription factors including interferon regulatory factor 3 (IRF3) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). Both IRF3 and NF-kB synergistically promote the immune response and the production of type I interferons (IFN-Is). Several viral proteins have been shown to modulate this response. The molecular mechanisms however are not understood