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PMID: 12208942 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Epstein-Barr virus mRNA export factor EB2 is essential for production of infectious virus.

Journal of virology ·Vol. 76 ·No. 19 ·2002-10-00 ·Pages 9635-44

Gruffat H, Batisse J, Pich D, Neuhierl B, Manet E, Hammerschmidt W, Sergeant A

Abstract

The splicing machinery which positions a protein export complex near the exon-exon junction mediates nuclear export of mRNAs generated from intron-containing genes. Many Epstein-Barr virus (EBV) early and late genes are intronless, and an alternative pathway, independent of splicing, must export the corresponding mRNAs. Since the EBV EB2 protein induces the cytoplasmic accumulation of intronless mRNA, it is tempting to speculate that EB2 is a viral adapter involved in the export of intronless viral mRNA. If this is true, then the EB2 protein is essential for the production of EBV infectious virions. To test this hypothesis, we generated an EBV mutant in which the BMLF1 gene, encoding the EB2 protein, has been deleted (EBV(BMLF1-KO)). Our studies show that EB2 is necessary for the production of infectious EBV and that its function cannot be transcomplemented by a cellular factor. In the EBV(BMLF1-KO) 293 cells, oriLyt-dependent DNA replication was greatly enhanced by EB2. Accordingly, EB2 induced the cytoplasmic accumulation of a subset of EBV early mRNAs coding for essential proteins implicated in EBV DNA replication during the productive cycle. Two herpesvirus homologs of the EB2 protein, the herpes simplex virus type 1 protein ICP27 and, the human cytomegalovirus protein UL69, only partly rescued the phenotype of the EBV(BMLF1-KO) mutant, indicating that some EB2 functions in virus production cannot be transcomplemented by ICP27 and UL69.

MeSH Terms
Active Transport, Cell Nucleus Amino Acid Sequence DNA Replication DNA-Binding Proteins/genetics DNA-Directed DNA Polymerase/genetics Herpesvirus 4, Human/physiology Molecular Sequence Data Phosphoproteins/physiology RNA, Messenger/analysis,metabolism Trans-Activators/physiology Viral Proteins/genetics,physiology Virus Replication
Chemicals
BALF2 protein, Human herpesvirus 4 DNA-Binding Proteins Phosphoproteins RNA, Messenger SM protein, Human herpesvirus 4 Trans-Activators Viral Proteins BALF5 protein, Epstein-barr virus DNA-Directed DNA Polymerase
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Gruffat Henri
Laboratoire de Virologie Humaine, INSERM U412, ENS-Lyon, F-69364 Lyon Cedex 07, France. hgruffat@ens-lyons.fr
Batisse Julien
Pich Dagmar
Neuhierl Bernhard
Manet Evelyne
Hammerschmidt Wolfgang
Sergeant Alain
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/jvi.76.19.9635-9644.2002
Email
hgruffat@ens-lyons.fr
Published
2002-10-00
Pages
9635-44
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC136519
Subset
IM
External Links
PubMed source DOI: 10.1128/jvi.76.19.9635-9644.2002 PMC Full Text View journal details
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