A major EBNA1 variant from Asian EBV isolates shows enhanced transcriptional activity compared to prototype B95.8.
Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1) has an instrumental role in maintaining EBV latent infection by controlling EBV episome replication and regulating viral transcription. It is a ubiquitously expressed protein during latent viral infection and in EBV-associated tumors. The EBNA1 C-terminus interacts functionally with the Qp and Cp that control viral gene expression in latency I/II and III, respectively. EBNA1 has been classified into five subtypes due to sequence variation in the DNA-interacting C-terminus. By DNA sequence analysis of its C-terminus, we detected a main sub-variant (V-val-v1) of EBNA1 with valine located in both positions 487 and 528 from matched samples including NPC biopsies and peripheral blood taken from Vietnamese (9), Chinese (12) NPC patients and healthy donors (5). In the FR-region of oriP from nine NPC biopsies from Vietnam we also frequently found substitutions, deletions and variable numbers of repeats. Using a luciferase reporter system, EBNA1 and FR both derived from Asian isolates induced higher transcriptional activity than those from B95-8 virus.
Do
Nguyen-Van
NV
Department of Microbiology, Tumor and Cell Biology , Karolinska Institutet, S-171 77 Stockholm, Sweden. Do.Nguyen.Van@ki.se
Ingemar
Ernberg
E
Phi
Phan-Thi Phi
PT
Jenny
Almqvist
A
Chinh
Tran-Thi
TT
Zeng
Yixin
Y
Hu
Lifu
L
D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D002681:China; D020031:Epstein-Barr Virus Infections / Q000821:virology*; D019309:Epstein-Barr Virus Nuclear Antigens / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017930:Genes, Reporter; D014644:Genetic Variation; D004854:Herpesvirus 4, Human / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D009154:Mutation; D009303:Nasopharyngeal Neoplasms / Q000821:virology*; D020218:Response Elements; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D015534:Trans-Activators / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation; D014744:Vietnam
D019309:Epstein-Barr Virus Nuclear Antigens; D015534:Trans-Activators; C417029:EBV-encoded nuclear antigen 1