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Journal of Virology, April 2007, p. 3677-3684, Vol. 81, No. 8
0022-538X/07/$08.00+0     doi:10.1128/JVI.01360-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

MDA-5 Is Cleaved in Poliovirus-Infected Cells{triangledown}

Paola M. Barral,1 Juliet M. Morrison,2 Jennifer Drahos,2 Pankaj Gupta,1 Devanand Sarkar,1,3 Paul B. Fisher,1,3,4,5 and Vincent R. Racaniello2*

Departments of Urology,1 Pathology,3 Neurosurgery,4 Microbiology,2 Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, College of Physicians & Surgeons, 701 W. 168th St. New York, New York 100325

Received 27 June 2006/ Accepted 18 January 2007

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 ~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.


* Corresponding author. Mailing address: Department of Microbiology, Columbia University Medical Center, College of Physicians & Surgeons, 701 W. 168th St., New York, NY 10032. Phone: (212) 305-5707. Fax: (212) 305-5106. E-mail: vrr1{at}columbia.edu

{triangledown} Published ahead of print on 31 January 2007.


Journal of Virology, April 2007, p. 3677-3684, Vol. 81, No. 8
0022-538X/07/$08.00+0     doi:10.1128/JVI.01360-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.




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