Epstein-Barr viral latency is disrupted by the immediate-early BRLF1 protein through a cell-specific mechanism.
Epstein-Barr virus (EBV), the causative agent of infectious mononucleosis, is a human herpesvirus associated with epithelial cell malignancies (nasopharyngeal carcinoma) as well as B-cell malignancies. Understanding how viral latency is disrupted is a central issue in herpesvirus biology. Epithelial cells are the major site of lytic EBV replication within the human host, and viral reactivation occurs in EBV-associated nasopharyngeal carcinomas. It is known that expression of a single viral immediate-early protein, BZLF1, is sufficient to initiate the switch from latent to lytic infection in B cells. Cellular regulation of BZLF1 transcription is therefore thought to play a key role in regulating the stringency of viral latency. Here we show that, unexpectedly, expression of another viral immediate-early protein, BRLF1, can disrupt viral latency in an epithelial cell-specific fashion. Therefore, the mechanisms leading to disruption of EBV latency appear to be cell-type specific.
Zalani
S
S
Department of Medicine, University of North Carolina 27599, USA.
Holley-Guthrie
E
E
Kenney
S
S
D000234:Adenoids / Q000166:cytology / Q000821:virology*; D001402:B-Lymphocytes / Q000166:cytology / Q000821:virology*; D002051:Burkitt Lymphoma / Q000209:etiology / Q000821:virology; D002277:Carcinoma / Q000209:etiology / Q000821:virology; D002472:Cell Transformation, Viral; D004268:DNA-Binding Proteins / Q000378:metabolism; D004847:Epithelial Cells; D004848:Epithelium / Q000821:virology; D004854:Herpesvirus 4, Human / Q000254:growth & development*; D006801:Humans; D017874:Immediate-Early Proteins / Q000378:metabolism*; D008957:Models, Genetic; D009303:Nasopharyngeal Neoplasms / Q000209:etiology / Q000821:virology; D009375:Neoplasms, Glandular and Epithelial / Q000209:etiology / Q000821:virology; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured; D014764:Viral Proteins; D017735:Virus Latency
C068382:BRLF1 protein, Human herpesvirus 4; C063676:BZLF1 protein, Herpesvirus 4, Human; D004268:DNA-Binding Proteins; D017874:Immediate-Early Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D014764:Viral Proteins