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Positive transcription elongation factor b (P-TEFb) contributes to dengue virus-stimulated induction of interleukin-8 (IL-8).

Abstract
Dengue virus (DENV) is one of the most common infectious pathogens worldwide. One major clinical and pathogenic feature of DENV infection is the elevation of interleukin-8 (IL-8) expression; however, little is known about the molecular mechanism of DENV-induced chemokine production. The positive transcription elongation factor b (P-TEFb) composed of CDK9 and cyclin T1 stimulates gene expression by enhancing RNA polymerase II (RNA pol II) processivity. This study examined the possibility that P-TEFb mediates DENV-induced IL-8 expression. The treatment of either a pharmacological inhibitor of P-TEFb, 5,6-dichloro-1-β-D-ribofuranosylbenzimidazole (DRB) or cyclin T1 siRNA prior to DENV infection abolished the elevation of IL-8, indicating that P-TEFb is essential for IL-8 induction. Moreover, DENV core protein participated in the activation of IL-8 promoter in a P-TEFb-dependent manner. Immunostaining and co-immunoprecipitation assays demonstrated the association between P-TEFb and DENV core protein. Finally, chromatin immunoprecipitation (ChIP) results indicated that P-TEFb and DENV core protein were recruited to the transcriptionally active IL-8 gene promoter. Taken together, this study showed that P-TEFb and DENV core protein work in concert to enhance IL-8 gene expression by DENV infection. This is the first demonstration of P-TEFb being directly involved in virus-induced host gene expression by interacting with a viral structural protein.
AuthorsLi-li Li, Shiau-Ting Hu, Shao-Hung Wang, Hsing-Hui Lee, Yen-Ting Wang, Yueh-Hsin Ping
JournalCellular microbiology (Cell Microbiol) Vol. 12 Issue 11 Pg. 1589-603 (Nov 2010) ISSN: 1462-5822 [Electronic] England
PMID20618343 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright© 2010 Blackwell Publishing Ltd.
Chemical References
  • Cyclin T
  • Interleukin-8
  • NF-kappa B
  • RNA, Small Interfering
  • Viral Core Proteins
  • Dichlororibofuranosylbenzimidazole
  • Positive Transcriptional Elongation Factor B
  • Cyclin-Dependent Kinase 9
  • RNA Polymerase II
Topics
  • Cell Line, Tumor
  • Cell Nucleus (metabolism)
  • Chromatin Immunoprecipitation
  • Cyclin T (genetics)
  • Cyclin-Dependent Kinase 9 (genetics, metabolism)
  • Dengue Virus (genetics, physiology)
  • Dichlororibofuranosylbenzimidazole (pharmacology)
  • Gene Expression Regulation
  • Humans
  • Interleukin-8 (biosynthesis, blood, genetics)
  • Mutation
  • NF-kappa B (metabolism)
  • Polymerase Chain Reaction
  • Positive Transcriptional Elongation Factor B (antagonists & inhibitors, genetics, metabolism)
  • Promoter Regions, Genetic
  • RNA Polymerase II (genetics, metabolism)
  • RNA, Small Interfering
  • Transcription, Genetic
  • Viral Core Proteins (genetics, metabolism)

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