Positive transcription elongation factor b (P-TEFb) contributes to dengue virus-stimulated induction of interleukin-8 (IL-8).
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.
Li
Li-li
LL
Institute of Microbiology and Immunology, National Yang-Ming University, Taipei, Taiwan.
Hu
Shiau-Ting
ST
Wang
Shao-Hung
SH
Lee
Hsing-Hui
HH
Wang
Yen-Ting
YT
Ping
Yueh-Hsin
YH
D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D047369:Chromatin Immunoprecipitation; D056906:Cyclin T / Q000235:genetics; D042863:Cyclin-Dependent Kinase 9 / Q000235:genetics / Q000378:metabolism; D003716:Dengue Virus / Q000235:genetics / Q000502:physiology*; D004004:Dichlororibofuranosylbenzimidazole / Q000494:pharmacology; D005786:Gene Expression Regulation; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis / Q000097:blood / Q000235:genetics*; D009154:Mutation; D016328:NF-kappa B / Q000378:metabolism; D016133:Polymerase Chain Reaction; D042925:Positive Transcriptional Elongation Factor B / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D012319:RNA Polymerase II / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering; D014158:Transcription, Genetic; D014758:Viral Core Proteins / Q000235:genetics / Q000378:metabolism*
D056906:Cyclin T; D016209:Interleukin-8; D016328:NF-kappa B; D034741:RNA, Small Interfering; D014758:Viral Core Proteins; D004004:Dichlororibofuranosylbenzimidazole; D042925:Positive Transcriptional Elongation Factor B; D042863:Cyclin-Dependent Kinase 9; D012319:RNA Polymerase II