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

Li li Li, Shiau Ting Hu, Shao Hung Wang, Hsing Hui Lee, Yen Ting Wang, Yueh Hsin Ping*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

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.

Original languageEnglish
Pages (from-to)1589-1603
Number of pages15
JournalCellular Microbiology
Volume12
Issue number11
DOIs
StatePublished - Nov 2010

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