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Journal of Virology, January 1999, p. 718-727, Vol. 73, No. 1
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Cleavage of Poly(A)-Binding Protein by Enterovirus
Proteases Concurrent with Inhibition of Translation In Vitro
Michelle
Joachims,
Pieter C.
Van Breugel,
and
Richard E.
Lloyd*
Department of Microbiology and Immunology,
University of Oklahoma Health Sciences Center, Oklahoma City,
Oklahoma 73104
Received 11 June 1998/Accepted 11 October 1998
Many enteroviruses, members of the family
Picornaviridae, cause a rapid and drastic inhibition of
host cell protein synthesis during infection, a process referred to as
host cell shutoff. Poliovirus, one of the best-studied enteroviruses,
causes marked inhibition of host cell translation while preferentially
allowing translation of its own genomic mRNA. An abundance of
experimental evidence has accumulated to indicate that cleavage of an
essential translation initiation factor, eIF4G, during infection is
responsible at least in part for this shutoff. However, evidence from
inhibitors of viral replication suggests that an additional event is
necessary for the complete translational shutoff observed during
productive infection. This report examines the effect of poliovirus
infection on a recently characterized 3' end translational stimulatory
protein, poly(A)-binding protein (PABP). PABP is involved in
stimulating translation initiation in lower eukaryotes by its
interaction with the poly(A) tail on mRNAs and has been proposed to
facilitate 5'-end-3'-end interactions in the context of the
closed-loop translational model. Here, we show that PABP is
specifically degraded during poliovirus infection and that it is
cleaved in vitro by both poliovirus 2A and 3C proteases and
coxsackievirus B3 2A protease. Further, PABP cleavage by 2A protease is
accompanied by concurrent loss of translational activity in an in
vitro-translation assay. Similar loss of translational activity also
occurs simultaneously with partial 3C protease-mediated cleavage of
PABP in translation assays. Further, PABP is not degraded during
infections in the presence of guanidine-HCl, which blocks the complete
development of host translation shutoff. These results provide
preliminary evidence that cleavage of PABP may contribute to inhibition
of host translation in infected HeLa cells, and they are consistent
with the hypothesis that PABP plays a role in facilitating translation
initiation in higher eukaryotes.
*
Corresponding author. Mailing address: Department of
Microbiology and Immunology, University of Oklahoma Health Sciences
Center, Oklahoma City, OK 73104. Phone: (405) 271-2889. Fax: (405)
271-5440. E-mail: richard-lloyd{at}ouhsc.edu.

Present address: Department of Molecular Cell Biology, University
of Utrecht, 3584 CH Utrecht, The
Netherlands.
Journal of Virology, January 1999, p. 718-727, Vol. 73, No. 1
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
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