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antiviral action of type I interferon (IFN) PMID: 17307033 A pair of dsRNA-binding domains in the N-terminal portion of PKR binds to dsRNA. PMID: 17307033,15961631,16043704 The TLR3 ectodomain senses dsRNA both extracellularly and in endosomes, and its structure has been solved recently PMID: 17307033 A pair of dsRNA-binding domains in the N-terminal portion of PKR binds to dsRNA. PKR functions to phosphorylate the a subunit of the translation initiation factor eIF2, thereby inhibiting protein synthesisA pair of dsRNA-binding domains in the N-terminal portion of PKR binds to dsRNA. PKR functions to phosphorylate the a subunit of the translation initiation factor eIF2, thereby inhibiting protein synthesis PMID: 17307033,15961631,16043704 The TLR3 ectodomain senses dsRNA both extracellularly and in endosomes, and its structure has been solved recently PMID: 17307033 Single-stranded RNA of ssRNA viruses is detected through TLR7 and TLR8, which are located in the endosomal compartment PMID: 17307033 Single-stranded RNA of ssRNA viruses is detected through TLR7 and TLR8, which are located in the endosomal compartment PMID: 17307033,17038590 Artificial capping or base modification of this 50-triphosphate (as would occur in host RNA) abolished this response, which they showed was mediated by direct binding to RIG-I PMID: 17307033 Moreover, they found that ssRNA such as that from the influenza virus genome, which is uncapped and has a 50-triphosphate moiety, associated with and activated RIG-I. PMID: 17307033,16672351,16625202,16714379 However, a current paradox is that, although negative-stranded paramyxoviruses do not produce detectable amounts of dsRNA, and are detected by RIG-I and not MDA5 their V proteins bind to Mda5 (and not RIG-I) and inhibit downstream signaling PMID: 17307033,17038589 The Pichlmair study also demonstrated that the IAV NS1 protein, which was thought to block IFN induction by sequestering dsRNA, instead blocks by forming a complex with RIG-I to abrogate RIG-I signaling indirect PMID: 17307033,17038589 The Pichlmair study also demonstrated that the IAV NS1 protein, which was thought to block IFN induction by sequestering dsRNA, instead blocks by forming a complex with RIG-I to abrogate RIG-I signaling indirect PMID: 17303033 Therefore, during infection, RIG-I probably mediates local IFNa production, which is crucial for the initial antiviral response, whereas TLR7 controls systemic IFNa levels, as pDCs make a substantial contribution to the total IFNa produced during an infection. PMID: 17303033,17008311 An additional antiviral effector mechanism involves the production of the inflammatory cytokines interleukin (IL)-1 and IL-18, which are generated by proteolytic processing of their pro-forms through the action of caspase-1 PMID: 17303033,17008311 An additional antiviral effector mechanism involves the production of the inflammatory cytokines interleukin (IL)-1 and IL-18, which are generated by proteolytic processing of their pro-forms through the action of caspase-1 indirect indiirect PMID: 17307033,17008311 Poly(I:C), viral dsRNA and Sendai virus (SeV) all activated caspase-1 through the nucleotide oligomerization domainlike receptor protein Nalp3 (also known as cryopyrin) indirect indirect PMID: 17307033,17008311 Poly(I:C), viral dsRNA and Sendai virus (SeV) all activated caspase-1 through the nucleotide oligomerization domainlike receptor protein Nalp3 (also known as cryopyrin) PMID: 17307033 Moreover, they found that ssRNA such as that from the influenza virus genome, which is uncapped and has a 50-triphosphate moiety, associated with and activated RIG-I.