Open AccessEBNA2 and Activated Notch Induce Expression of BATF
Author(s) -
Lisa M. Johansen,
Christopher D. Deppmann,
Kimberly D. Erickson,
William F. Coffin,
Tina M. Thornton,
Sean E. Humphrey,
Jennifer Martin,
Elizabeth J. Taparowsky
Publication year - 2003
Publication title -
journal of virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.617
H-Index - 292
eISSN - 1070-6321
pISSN - 0022-538X
DOI - 10.1128/jvi.77.10.6029-6040.2003
Subject(s) - biology , lytic cycle , transactivation , bzlf1 , epstein–barr virus , gene , microbiology and biotechnology , virus latency , gene expression , genetics , viral replication , virus , herpesviridae , viral disease
The immortalization of human B lymphocytes by Epstein-Barr virus (EBV) requires the virus-encoded transactivator EBNA2 and the products of both viral and cellular genes which serve as EBNA2 targets. In this study, we identified BATF as a cellular gene that is up-regulated dramatically within 24 h following the infection of established and primary human B cells with EBV. The transactivation of BATF is mediated by EBNA2 in a B-cell-specific manner and is duplicated in non-EBV-infected B cells by the expression of mammalian Notch proteins. In contrast to other target genes activated by EBNA2, the BATF gene encodes a member of the AP-1 family of transcription factors that functions as a negative regulator of AP-1 activity and as an antagonist of cell growth. A potential role for BATF in promoting EBV latency is supported by studies in which BATF was shown to negatively impact the expression of a BZLF1 reporter gene and to reduce the frequency of lytic replication in latently infected cells. The identification of BATF as a cellular target of EBV provides important new information on how programs of viral and cellular gene expression may be coordinated to promote viral latency and control lytic-cycle entry.