17267501

pubmed:Citation

8

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.

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http://linkedlifedata.com/resource/pubmed/journal/0113724

http://linkedlifedata.com/resource/pubmed/chemical/3C proteases, http://linkedlifedata.com/resource/pubmed/chemical/Caspases, http://linkedlifedata.com/resource/pubmed/chemical/Cysteine Endopeptidases, http://linkedlifedata.com/resource/pubmed/chemical/DEAD-box RNA Helicases, http://linkedlifedata.com/resource/pubmed/chemical/IFIH1 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/PARP1 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Poly(ADP-ribose) Polymerases, http://linkedlifedata.com/resource/pubmed/chemical/Proteasome Endopeptidase Complex, http://linkedlifedata.com/resource/pubmed/chemical/Viral Proteins, http://linkedlifedata.com/resource/pubmed/chemical/picornain 2A, Picornavirus

Apr

pubmed-author:BarralPaola MPM, pubmed-author:DrahosJenniferJ, pubmed-author:FisherPaul BPB, pubmed-author:GuptaPankajP, pubmed-author:MorrisonJuliet MJM, pubmed-author:RacanielloVincent RVR, pubmed-author:SarkarDevanandD

81

Y

2009-11-19

2007

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.