EBNA2 is required for protection of latently Epstein-Barr virus-infected B cells against specific apoptotic stimuli.
In addition to functioning as a transcriptional transactivator, Epstein-Barr virus EBNA2 interacts with Nur77 to protect against Nur77-mediated apoptosis. Estrogen-regulated EBNA2 in EREB2-5 cells was replaced by either EBNA2 or EBNA2 with a deletion of conserved region 4 (EBNA2DeltaCR4). Both EBNA2-converted and EBNA2DeltaCR4-converted EREB2-5 cells grew in the absence of estrogen and expressed LMP1. Treatment with tumor necrosis factor alpha did not induce apoptosis of EBNA2- or EBNA2DeltaCR4-expressing cells, but EBNA2DeltaCR4 cells were susceptible to etoposide and 5-fluorouracil, Nur77-mediated inducers of apoptosis. Thus, EBNA2 protects B cells against specific apoptotic agents against which LMP1 is not effective.
Lee
Jae Myun
JM
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, School of Medicine, Bunting-Blaustein Building CRB308, 1650 Orleans Street, Baltimore, MD 21231, USA.
Lee
Kyoung-Ho
KH
Farrell
Christopher J
CJ
Ling
Paul D
PD
Kempkes
Bettina
B
Park
Jeon Han
JH
Hayward
S Diane
SD
D017209:Apoptosis; D001402:B-Lymphocytes / Q000166:cytology / Q000821:virology*; D004268:DNA-Binding Proteins / Q000502:physiology; D019309:Epstein-Barr Virus Nuclear Antigens / Q000502:physiology*; D004854:Herpesvirus 4, Human / Q000502:physiology*; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D014157:Transcription Factors / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014763:Viral Matrix Proteins / Q000502:physiology; D014764:Viral Proteins; D017735:Virus Latency
D004268:DNA-Binding Proteins; C402641:EBNA-2 protein, Human herpesvirus 4; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D019309:Epstein-Barr Virus Nuclear Antigens; C539821:NR4A1 protein, human; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D014763:Viral Matrix Proteins; D014764:Viral Proteins