Abstract |
Epstein-Barr virus (EBV) establishes a latent form of infection in memory B cells, while antibody-secreting plasma cells often harbor the lytic form of infection. The switch between latent and lytic EBV infection is mediated by the two viral immediate-early proteins BZLF1 (Z) and BRLF1 (R), which are not expressed in latently infected B cells. Here we demonstrate that a cellular transcription factor that plays an essential role in plasma cell differentiation, X-box-binding protein 1 (XBP-1), also activates the transcription of the two EBV immediate-early gene promoters. In reporter gene assays, XBP-1 alone was sufficient to activate the R promoter, whereas the combination of XBP-1 and protein kinase D (PKD) was required for efficient activation of the Z promoter. Most importantly, the expression of XBP-1 and activated PKD was sufficient to induce lytic viral gene expression in EBV-positive nasopharyngeal carcinoma cells and lymphoblastoid cells, while an XBP-1 small interfering RNA inhibited constitutive lytic EBV gene expression in lymphoblastoid cells. These results suggest that the plasma cell differentiation factor XBP-1, in combination with activated PKD, can mediate the reactivation of EBV, thereby allowing the viral life cycle to be intimately linked to plasma cell differentiation.
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Authors | Prasanna M Bhende, Sarah J Dickerson, Xiaoping Sun, Wen-Hai Feng, Shannon C Kenney |
Journal | Journal of virology
(J Virol)
Vol. 81
Issue 14
Pg. 7363-70
(Jul 2007)
ISSN: 0022-538X [Print] United States |
PMID | 17494074
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Chemical References |
- DNA Primers
- DNA-Binding Proteins
- Nuclear Proteins
- RNA, Small Interfering
- Regulatory Factor X Transcription Factors
- Transcription Factors
- X-Box Binding Protein 1
- XBP1 protein, human
- Valproic Acid
- protein kinase D
- Protein Kinase C
- CAMK4 protein, human
- Calcium-Calmodulin-Dependent Protein Kinase Type 4
- Calcium-Calmodulin-Dependent Protein Kinases
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Topics |
- Base Sequence
- Calcium-Calmodulin-Dependent Protein Kinase Type 4
- Calcium-Calmodulin-Dependent Protein Kinases
(metabolism)
- Cell Line, Tumor
- DNA Primers
- DNA-Binding Proteins
(physiology)
- Electrophoretic Mobility Shift Assay
- Enzyme Activation
- Gene Expression Regulation, Viral
(physiology)
- Genes, Viral
- Herpesvirus 4, Human
(genetics, physiology)
- Humans
- Nuclear Proteins
(physiology)
- Protein Kinase C
(metabolism)
- RNA, Small Interfering
- Regulatory Factor X Transcription Factors
- Transcription Factors
- Valproic Acid
(pharmacology)
- Virus Activation
(drug effects)
- Virus Latency
- X-Box Binding Protein 1
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