Unknown

Dataset Information

0

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


ABSTRACT: DNA viruses such as herpesviruses are known to encode homologs of cellular antiapoptotic viral Bcl-2 proteins (vBcl-2s), 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.

SUBMITTER: Altmann M 

PROVIDER: S-EPMC1283332 | biostudies-literature |

REPOSITORIES: biostudies-literature

Similar Datasets

| S-EPMC3009601 | biostudies-literature
| S-EPMC3066549 | biostudies-other
| PRJNA794826 | ENA
| S-EPMC6451101 | biostudies-literature
| S-EPMC6321917 | biostudies-literature
2018-07-12 | GSE116675 | GEO
| S-EPMC5597738 | biostudies-literature
| S-EPMC6095625 | biostudies-literature
| S-EPMC3234233 | biostudies-other
2018-10-14 | GSE119823 | GEO