title: RIG-I is cleaved during picornavirus infection.
abstract: The innate immune system senses RNA virus infections through membrane-bound Toll-like receptors or the cytoplasmic proteins RIG-I and MDA-5. RIG-I is believed to recognize the 5'-triphosphate present on many viral RNAs, and hence is important for sensing infections by paramyxoviruses, influenza viruses, rhabdoviruses, and flaviviruses. MDA-5 recognizes dsRNA, and senses infection with picornaviruses, whose RNA 5'-ends are linked to a viral protein, VPg, not a 5'-triphosphate. We previously showed that MDA-5 is degraded in cells infected with different picornaviruses, and suggested that such cleavage might be a mechanism to antagonize production of type I IFN in response to viral infection. Here we examined the state of RIG-I during picornavirus infection. RIG-I is degraded in cells infected with poliovirus, rhinoviruses, echovirus, and encephalomyocarditis virus. In contrast to MDA-5, cleavage of RIG-I is not accomplished by cellular caspases or the proteasome. Rather, the viral proteinase 3C(pro) cleaves RIG-I, both in vitro and in cells. Cleavage of RIG-I during picornavirus infection may constitute another mechanism for attenuating the innate response to viral infection.
authors.affiliation: Department of Human and Molecular Genetics, Virginia Commonwealth University School of Medicine, 1101 East Marshall Street, Sanger Hall Building, Room 11-015, Richmond, VA 23298-0033, USA.
authors.forename: Paola M
authors.initials: PM
authors.lastname: Barral
authors.forename: Devanand
authors.initials: D
authors.lastname: Sarkar
authors.forename: Paul B
authors.initials: PB
authors.lastname: Fisher
authors.forename: Vincent R
authors.initials: VR
authors.lastname: Racaniello
mesh_terms: D000086042:3C Viral Proteases; D002460:Cell Line; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000378:metabolism*; D006801:Humans; D010849:Picornaviridae / Q000276:immunology* / Q000502:physiology*; D011971:Receptors, Immunologic; D014764:Viral Proteins / Q000378:metabolism*
chemical_list: D011971:Receptors, Immunologic; D014764:Viral Proteins; D003546:Cysteine Endopeptidases; D000086042:3C Viral Proteases; C452820:RIGI protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases