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Journal of Virology, September 2007, p. 8919-8932, Vol. 81, No. 17
0022-538X/07/$08.00+0     doi:10.1128/JVI.01013-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Cellular Protein Modification by Poliovirus: the Two Faces of Poly(rC)-Binding Protein{triangledown}

Rushika Perera,{dagger} Sarah Daijogo, Brandon L. Walter,{ddagger} Joseph H. C. Nguyen, and Bert L. Semler*

Department of Microbiology and Molecular Genetics, School of Medicine, University of California, Irvine, California 92697-4025

Received 9 May 2007/ Accepted 12 June 2007

During picornavirus infection, several cellular proteins are cleaved by virus-encoded proteinases. Such cleavage events are likely to be involved in the changing dynamics during the intracellular viral life cycle, from viral translation to host shutoff to RNA replication to virion assembly. For example, it has been proposed that there is an active switch from poliovirus translation to RNA replication mediated by changes in RNA-binding protein affinities. This switch could be a mechanism for controlling template selection for translation and negative-strand viral RNA synthesis, two processes that use the same positive-strand RNA as a template but proceed in opposing directions. The cellular protein poly(rC)-binding protein (PCBP) was identified as a primary candidate for regulating such a mechanism. Among the four different isoforms of PCBP in mammalian cells, PCBP2 is required for translation initiation on picornavirus genomes with type I internal ribosome entry site elements and also for RNA replication. Through its three K-homologous (KH) domains, PCPB2 forms functional protein-protein and RNA-protein complexes with components of the viral translation and replication machinery. We have found that the isoforms PCBP1 and -2 are cleaved during the mid-to-late phase of poliovirus infection. On the basis of in vitro cleavage assays, we determined that this cleavage event was mediated by the viral proteinases 3C/3CD. The primary cleavage occurs in the linker between the KH2 and KH3 domains, resulting in truncated PCBP2 lacking the KH3 domain. This cleaved protein, termed PCBP2-{Delta}KH3, is unable to function in translation but maintains its activity in viral RNA replication. We propose that through the loss of the KH3 domain, and therefore loss of its ability to function in translation, PCBP2 can mediate the switch from viral translation to RNA replication.

* Corresponding author. Mailing address: Department of Microbiology and Molecular Genetics, School of Medicine, Med Sci B240, University of California, Irvine, CA 92697. Phone: (949) 824-7573. Fax: (949) 824-2694. E-mail: blsemler{at}uci.edu

{triangledown} Published ahead of print on 20 June 2007.

{dagger} Present address: Department of Biological Sciences, Purdue University, West Lafayette, IN 47907.

{ddagger} Present address: Rocky Mountain Laboratories, Hamilton, MT 59840.

Journal of Virology, September 2007, p. 8919-8932, Vol. 81, No. 17
0022-538X/07/$08.00+0     doi:10.1128/JVI.01013-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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