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PMID: 18632855 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Cleavage of poly(A)-binding protein by poliovirus 3C proteinase inhibits viral internal ribosome entry site-mediated translation.

Journal of virology ·Vol. 82 ·No. 19 ·2008-10-00 ·Pages 9389-99

Bonderoff JM, Larey JL, Lloyd RE

Abstract

The two enteroviral proteinases, 2A proteinase (2A(pro)) and 3C proteinase (3C(pro)), induce host cell translation shutoff in enterovirus-infected cells by cleaving canonical translation initiation factors. Cleavage of poly(A)-binding protein (PABP) by 3C(pro) has been shown to be a necessary component for host translation shutoff. Here we show that 3C(pro) 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 2A(pro) on IRES translation, and 3C(pro)-induced translation inhibition can be partially rescued by addition of recombinant PABP in vitro. 3C(pro) 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 3C(pro) 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.

MeSH Terms
3C Viral Proteases Cysteine Endopeptidases/chemistry Gene Expression Regulation, Viral HeLa Cells Humans Models, Biological Models, Genetic Mutation Peptide Initiation Factors/chemistry Poly A/chemistry Poly(A)-Binding Proteins/genetics Protein Biosynthesis RNA, Viral/genetics,metabolism Recombinant Proteins/chemistry Ribosomes/genetics Viral Proteins/chemistry
Chemicals
Peptide Initiation Factors Poly(A)-Binding Proteins RNA, Viral Recombinant Proteins Viral Proteins Poly A Cysteine Endopeptidases 3C Viral Proteases 3C proteases
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Bonderoff Jennifer M
Department of Molecular Virology and Microbiology, 860E, One Baylor Plaza, Houston, TX 77030, USA.
Larey Jennifer L
Lloyd Richard E
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
1098-5514
DOI
10.1128/JVI.00006-08
Published
2008-10-00
Epub
2008-00-16
Pages
9389-99
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC2546981
Subset
IM
Grants
NIAID NIH HHS · R56 AI050237 · United States
NIAID NIH HHS · R01 AI050237 · United States
NIAID NIH HHS · AI50237 · United States
NIGMS NIH HHS · R01 GM059803 · United States
NIGMS NIH HHS · GM59803 · United States
External Links
PubMed source DOI: 10.1128/JVI.00006-08 PMC Full Text View journal details
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