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PMID: 11752411 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Control of Epstein-Barr virus reactivation by activated CD40 and viral latent membrane protein 1.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 99 ·No. 1 ·2002-01-08 ·Pages 437-42

Adler B, Schaadt E, Kempkes B, Zimber-Strobl U, Baier B, Bornkamm GW

Abstract

In humans, Epstein-Barr virus (EBV) establishes a persistent latent infection in peripheral resting B lymphocytes. Virus reactivation is highly restricted. Whereas in healthy humans the infection usually is benign, immunocompromised patients show an increased risk for EBV-associated malignancies, accompanied by an increase in virus replication and in the number of virus-infected cells. To search for viral and host factors regulating virus reactivation, we used conditionally EBV-immortalized B cells. We found that CD40-CD40 ligand interaction and the viral mimic of activated CD40, EBV latent membrane protein 1, suppress virus reactivation. Both inhibit anti-IgM or phorbolester-induced transcription of the viral immediate early protein BZLF1, which controls entry into the viral lytic cycle. The finding that latent membrane protein 1 and CD40 contribute to the regulation of latency may have important implications for the balance between EBV and its host in normal as well as in immunocompromised individuals.

MeSH Terms
B-Lymphocytes/virology Blotting, Northern CD40 Antigens/biosynthesis,metabolism Cell Line Cell Separation DNA-Binding Proteins/physiology Flow Cytometry Herpesvirus 4, Human/metabolism Humans Immunoblotting Ligands Protein Binding Signal Transduction Trans-Activators/physiology Transcription, Genetic Transfection Viral Matrix Proteins/metabolism Viral Proteins
Chemicals
BZLF1 protein, Herpesvirus 4, Human CD40 Antigens DNA-Binding Proteins EBV-associated membrane antigen, Epstein-Barr virus Ligands Trans-Activators Viral Matrix Proteins Viral Proteins
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Adler Barbara
GSF-National Research Center for Environment and Health, Institute for Clinical Molecular Biology and Tumor Genetics, Marchioninistrasse 25, D-81377 Munich, Germany. b.adler@gsf.de
Schaadt Eveline
Kempkes Bettina
Zimber-Strobl Ursula
Baier Barbara
Bornkamm Georg W
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.221439999
Email
b.adler@gsf.de
Published
2002-01-08
Epub
2001-00-18
Pages
437-42
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC117578
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.221439999 PMC Full Text View journal details
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