Expression of Epstein-Barr virus lytic gene BRLF1 in nasopharyngeal carcinoma: potential use in diagnosis.
Tumour cells of undifferentiated nasopharyngeal carcinoma (NPC) consistently harbour Epstein-Barr virus (EBV) genes. Expression of mRNA transcripts associated with EBV latency has been demonstrated in such cells. However, expression of EBV lytic genes has not been well elucidated, although various lines of evidence have suggested that there is EBV replication in NPC tumour cells. We have studied mRNA expression of representative EBV lytic genes by RT-PCR in nasopharynx biopsies obtained from NPC and control individuals. In both NPC and control biopsies, EBV lytic genes BZLF1, BALF2 and BCLF1 were detected readily. However, BRLF1 was detected in NPC biopsies only. The BRLF1 gene was then cloned and expressed in vitro, and the protein product, Rta, was used as an antigen to detect specific antibodies by immunoprecipitation in plasma samples obtained from NPC patients and healthy controls. IgG antibodies directed against Rta were detected in 44 of 53 NPC plasma samples (83.0%), but only in 1 of 53 control samples (1.9%). Furthermore, the antibody binding regions were found in the C-terminal two-thirds of Rta. This serological result confirms indirectly that BRLF1 is specifically expressed in NPC tumour cells. Rta might play an important role in NPC pathogenesis, considering its multiple functions in EBV replication and cell cycles. Moreover, the detection of IgG antibodies directed against Rta could be developed into a diagnostic parameter for NPC.
Feng
Ping
P
Department of Microbiology, Faculty of Medicine1 and Institute of Molecular Agrobiology2, National University of Singapore, Block MD4/4A, 5 Science Drive 2, Singapore 117597, Republic of Singapore.
Ren
Ee Chee
EC
Department of Microbiology, Faculty of Medicine1 and Institute of Molecular Agrobiology2, National University of Singapore, Block MD4/4A, 5 Science Drive 2, Singapore 117597, Republic of Singapore.
Liu
Dingxiang
D
Department of Microbiology, Faculty of Medicine1 and Institute of Molecular Agrobiology2, National University of Singapore, Block MD4/4A, 5 Science Drive 2, Singapore 117597, Republic of Singapore.
Chan
Soh Ha
SH
Department of Microbiology, Faculty of Medicine1 and Institute of Molecular Agrobiology2, National University of Singapore, Block MD4/4A, 5 Science Drive 2, Singapore 117597, Republic of Singapore.
Hu
Huaizhong
H
Department of Microbiology, Faculty of Medicine1 and Institute of Molecular Agrobiology2, National University of Singapore, Block MD4/4A, 5 Science Drive 2, Singapore 117597, Republic of Singapore.
D000918:Antibody Specificity; D002460:Cell Line; D020031:Epstein-Barr Virus Infections / Q000175:diagnosis / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D015967:Gene Expression Regulation, Viral; D004854:Herpesvirus 4, Human / Q000235:genetics*; D006801:Humans; D017874:Immediate-Early Proteins / Q000096:biosynthesis* / Q000235:genetics* / Q000276:immunology; D009303:Nasopharyngeal Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000821:virology; D016366:Open Reading Frames; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000096:biosynthesis* / Q000235:genetics* / Q000276:immunology; D014407:Tumor Cells, Cultured; D014764:Viral Proteins; D017735:Virus Latency
C068382:BRLF1 protein, Human herpesvirus 4; D017874:Immediate-Early Proteins; D012333:RNA, Messenger; D015534:Trans-Activators; D014764:Viral Proteins