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Journal of Virology, June 2008, p. 5847-5859, Vol. 82, No. 12
0022-538X/08/$08.00+0     doi:10.1128/JVI.01514-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Poliovirus 2APro Increases Viral mRNA and Polysome Stability Coordinately in Time with Cleavage of eIF4G{triangledown}

Brian J. Kempf1 and David J. Barton1,2*

Department of Microbiology,1 Program in Molecular Biology, University of Colorado Denver, School of Medicine, Aurora, Colorado 800452

Received 10 July 2007/ Accepted 28 March 2008

Poliovirus (PV) 2A protease (2APro) cleaves eukaryotic initiation factors 4GI and 4GII (eIF4GI and eIF4GII) within virus-infected cells, effectively halting cap-dependent mRNA translation. PV mRNA, which does not possess a 5' cap, is translated via cap-independent mechanisms within viral protease-modified messenger ribonucleoprotein (mRNP) complexes. In this study, we determined that 2APro activity was required for viral polysome formation and stability. 2APro cleaved eIF4GI and eIF4GII as PV polysomes assembled. A 2ACys109Ser (2APro with a Cys109Ser mutation) protease active site mutation that prevented cleavage of eIF4G coordinately inhibited the de novo formation of viral polysomes, the stability of viral polysomes, and the stability of PV mRNA within polysomes. 2ACys109Ser-associated defects in PV mRNA and polysome stability correlated with defects in PV mRNA translation. 3CPro activity was not required for viral polysome formation or stability. 2APro-mediated cleavage of eIF4G along with poly(rC) binding protein binding to the 5' terminus of uncapped PV mRNA appear to be concerted mechanisms that allow PV mRNA to form mRNP complexes that evade cellular mRNA degradation machinery.


* Corresponding author. Mailing address: Department of Microbiology, University of Colorado Denver, School of Medicine, Mail Stop 8333, RC1-North, P18-9116, 12800 East 19th Ave., Aurora, CO 80045. Phone: (303) 724-4215. Fax: (303) 724-4226. E-mail: david.barton{at}uchsc.edu

{triangledown} Published ahead of print on 9 April 2008.


Journal of Virology, June 2008, p. 5847-5859, Vol. 82, No. 12
0022-538X/08/$08.00+0     doi:10.1128/JVI.01514-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.




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