EBNA2 and activated Notch induce expression of BATF.
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.
Department of Biological Sciences, Purdue University, West Lafayette, Indiana 47907-1392, USA.
Lisa M
LM
Johansen
Christopher D
CD
Deppmann
Kimberly D
KD
Erickson
William F
WF
Coffin
Tina M
TM
Thornton
Sean E
SE
Humphrey
Jennifer M
JM
Martin
Elizabeth J
EJ
Taparowsky
D001402:B-Lymphocytes / Q000821:virology; D050976:Basic-Leucine Zipper Transcription Factors; D002460:Cell Line; D002478:Cells, Cultured; D019309:Epstein-Barr Virus Nuclear Antigens / Q000235:genetics / Q000378:metabolism*; D015967:Gene Expression Regulation, Viral; D006367:HeLa Cells; D004854:Herpesvirus 4, Human / Q000472:pathogenicity* / Q000502:physiology; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051880:Receptors, Notch; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014764:Viral Proteins; D017735:Virus Latency
D050976:Basic-Leucine Zipper Transcription Factors; C431772:Batf protein, mouse; C402641:EBNA-2 protein, Human herpesvirus 4; D019309:Epstein-Barr Virus Nuclear Antigens; D008565:Membrane Proteins; D051880:Receptors, Notch; D014157:Transcription Factors; D014764:Viral Proteins