Abstract
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.
Publication types
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Comparative Study
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adenoids / cytology
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Adenoids / virology*
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B-Lymphocytes / cytology
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B-Lymphocytes / virology*
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Burkitt Lymphoma / etiology
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Burkitt Lymphoma / virology
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Carcinoma / etiology
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Carcinoma / virology
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Cell Transformation, Viral
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DNA-Binding Proteins / metabolism
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Epithelial Cells
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Epithelium / virology
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Herpesvirus 4, Human / growth & development*
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Humans
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Immediate-Early Proteins / metabolism*
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Models, Genetic
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Nasopharyngeal Neoplasms / etiology
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Nasopharyngeal Neoplasms / virology
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Neoplasms, Glandular and Epithelial / etiology
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Neoplasms, Glandular and Epithelial / virology
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Trans-Activators / metabolism
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Transcription Factors / metabolism*
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Transcription, Genetic
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Transcriptional Activation
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Tumor Cells, Cultured
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Viral Proteins*
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Virus Latency*
Substances
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BRLF1 protein, Human herpesvirus 4
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BZLF1 protein, Herpesvirus 4, Human
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DNA-Binding Proteins
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Immediate-Early Proteins
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Trans-Activators
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Transcription Factors
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Viral Proteins