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Journal of Virology, October 2008, p. 9389-9399, Vol. 82, No. 19
0022-538X/08/$08.00+0     doi:10.1128/JVI.00006-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Cleavage of Poly(A)-Binding Protein by Poliovirus 3C Proteinase Inhibits Viral Internal Ribosome Entry Site-Mediated Translation{triangledown}

Jennifer M. Bonderoff,1,2 Jennifer L. LaRey,2 and Richard E. Lloyd1*

Department of Molecular Virology and Microbiology,1 Interdepartmental Program in Cell and Molecular Biology, Baylor College of Medicine, Houston, Texas 770302

Received 2 January 2008/ Accepted 10 July 2008

The two enteroviral proteinases, 2A proteinase (2Apro) and 3C proteinase (3Cpro), induce host cell translation shutoff in enterovirus-infected cells by cleaving canonical translation initiation factors. Cleavage of poly(A)-binding protein (PABP) by 3Cpro has been shown to be a necessary component for host translation shutoff. Here we show that 3Cpro inhibits cap-independent translation mediated by the poliovirus internal ribosome entry site (IRES) in a dose-dependent manner in HeLa translation extracts displaying cap-poly(A) synergy. This effect is independent of the stimulatory effect of 2Apro on IRES translation, and 3Cpro-induced translation inhibition can be partially rescued by addition of recombinant PABP in vitro. 3Cpro inhibits IRES translation on transcripts containing or lacking poly(A) tails, suggesting that cleavage of PABP and IRES trans-activating factors polypyrimidine tract-binding protein and poly r(C)-binding protein 2 may also be important for inhibition. Expression of 3Cpro cleavage-resistant PABP in cells increased translation of nonreplicating viral minigenome reporter RNAs during infection and also delayed and reduced virus protein synthesis from replicating RNA. Further, expression of cleavage-resistant PABP in cells reduced the accumulation of viral RNA and the output of infectious virus. These results suggest that cleavage of PABP contributes to viral translation shutoff that is required for the switch from translation to RNA replication.

* Corresponding author. Mailing address: Department of Molecular Virology and Microbiology, 860E, One Baylor Plaza, Houston, TX 77030. Phone: (713) 798-8993. Fax: (713) 798-5075. E-mail: rlloyd{at}bcm.edu

{triangledown} Published ahead of print on 16 July 2008.

Journal of Virology, October 2008, p. 9389-9399, Vol. 82, No. 19
0022-538X/08/$08.00+0     doi:10.1128/JVI.00006-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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