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X-box-binding protein 1 activates lytic Epstein-Barr virus gene expression in combination with protein kinase D.

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.
AuthorsPrasanna M Bhende, Sarah J Dickerson, Xiaoping Sun, Wen-Hai Feng, Shannon C Kenney
JournalJournal of virology (J Virol) Vol. 81 Issue 14 Pg. 7363-70 (Jul 2007) ISSN: 0022-538X [Print] United States
PMID17494074 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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
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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