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Altmann, M. ; Hammerschmidt, W.

Epstein-Barr Virus provides a new paradigm: A requirement for the immediate inhibition of apoptosis.

PLoS Biol. 3, 2148-2157:e404 (2005)
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DNA viruses such as herpesviruses are known to encode homologs of cellular antiapoptotic viral Bcl-2 proteins (vBcl2s), which protect the virus from apoptosis in its host cell during virus synthesis. Epstein-Barr virus (EBV), a human tumor virus and a prominent member of gamma-herpesviruses, infects primary resting B lymphocytes to establish a latent infection and yield proliferating, growth-transformed B cells in vitro. In these cells, 11 viral genes that contribute to cellular transformation are consistently expressed. EBV also encodes two vBcl-2 genes whose roles are unclear. Here we show that the genetic inactivation of both vBcl-2 genes disabled EBV's ability to transform primary resting B lymphocytes. Primary B cells infected with a vBcl-2-negative virus did not enter the cell cycle and died of immediate apoptosis. Apoptosis was abrogated in infected cells in which vBcl-2 genes were maximally expressed within the first 24 h postinfection. During latent infection, however, the expression of vBcl-2 genes became undetectable. Thus, both vBcl-2 homologs are essential for initial cellular transformation but become dispensable once a latent infection is established. Because long-lived, latently infected memory B cells and EBV-associated B-cell lymphomas are derived from EBV-infected proapoptotic germinal center B cells, we conclude that vBcl-2 genes are essential for the initial evasion of apoptosis in cells in vivo in which the virus establishes a latent infection or causes cellular transformation or both.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords NF-KAPPA-B; LYMPHOCYTE GROWTH TRANSFORMATION; MEMBRANE-PROTEIN 1; IN-VIVO; LATENT MEMBRANE-PROTEIN-1; ESCHERICHIA-COLI; CELL-DEATH; DNA-REPLICATION; BCL-2 PROTEINS; LYTIC ORIGIN
ISSN (print) / ISBN 1544-9173
e-ISSN 1545-7885
Journal PLoS Biology
Quellenangaben Volume: 3, Issue: 12, Pages: 2148-2157, Article Number: e404 Supplement: ,
Publisher Public Library of Science (PLoS)
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Research Unit Gene Vector (AGV)