title: MDA-5 is cleaved in poliovirus-infected cells.
abstract: Infections with RNA viruses are sensed by the innate immune system through membrane-bound Toll-like receptors or the cytoplasmic RNA helicases RIG-I and MDA-5. It is believed that MDA-5 is crucial for sensing infections by picornaviruses, but there have been no studies on the role of this protein during infection with poliovirus, the prototypic picornavirus. Beginning at 4 h postinfection, MDA-5 protein is degraded in poliovirus-infected cells. Levels of MDA-5 declined beginning at 6 h after infection with rhinovirus type 1a or encephalomyocarditis virus, but the protein was stable in cells infected with rhinovirus type 16 or echovirus type 1. Cleavage of MDA-5 is not carried out by either poliovirus proteinase 2Apro or 3Cpro. Instead, degradation of MDA-5 in poliovirus-infected cells occurs in a proteasome- and caspase-dependent manner. Degradation of MDA-5 during poliovirus infection correlates with cleavage of poly(ADP) ribose polymerase (PARP), a hallmark of apoptosis. Induction of apoptosis by puromycin leads to cleavage of both PARP and MDA-5. The MDA-5 cleavage product observed in cells treated with puromycin is approximately 90 kDa, similar in size to the putative cleavage product observed in poliovirus-infected cells. Poliovirus-induced cleavage of MDA-5 may be a mechanism to antagonize production of type I interferon in response to viral infection.
authors.affiliation: Department of Urology, and Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, College of Physicians & Surgeons, 701 W. 168th St., New York, NY 10032, USA.
authors.forename: Paola M
authors.initials: PM
authors.lastname: Barral
authors.forename: Juliet M
authors.initials: JM
authors.lastname: Morrison
authors.forename: Jennifer
authors.initials: J
authors.lastname: Drahos
authors.forename: Pankaj
authors.initials: P
authors.lastname: Gupta
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; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D003546:Cysteine Endopeptidases / Q000378:metabolism; D053487:DEAD-box RNA Helicases / Q000378:metabolism*; D004686:Encephalomyocarditis virus / Q000276:immunology; D029822:Enterovirus B, Human / Q000276:immunology; D006367:HeLa Cells; D006801:Humans; D000072640:Interferon-Induced Helicase, IFIH1; D017955:Poliovirus / Q000276:immunology*; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D012229:Rhinovirus / Q000276:immunology; D014764:Viral Proteins / Q000378:metabolism
chemical_list: D014764:Viral Proteins; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D020169:Caspases; D003546:Cysteine Endopeptidases; D000086042:3C Viral Proteases; C057400:picornain 2A, Picornavirus; D046988:Proteasome Endopeptidase Complex; C452815:IFIH1 protein, human; D053487:DEAD-box RNA Helicases; D000072640:Interferon-Induced Helicase, IFIH1