Curcumin inhibits herpes simplex virus immediate-early gene expression by a mechanism independent of p300/CBP histone acetyltransferase activity.
Curcumin, a phenolic compound from the curry spice turmeric, exhibits a wide range of activities in eukaryotic cells, including antiviral effects that are at present incompletely characterized. Curcumin is known to inhibit the histone acetyltransferase activity of the transcriptional coactivator proteins p300 and CBP, which are recruited to the immediate early (IE) gene promoters of herpes simplex virus type 1 (HSV-1) by the viral transactivator protein VP16. We tested the hypothesis that curcumin, by inhibiting these coactivators, would block viral infection and gene expression. In cell culture assays, curcumin significantly decreased HSV-1 infectivity and IE gene expression. Entry of viral DNA to the host cell nucleus and binding of VP16 to IE gene promoters was not affected by curcumin, but recruitment of RNA polymerase II to those promoters was significantly diminished. However, these effects were observed using lower curcumin concentrations than those required to substantially inhibit global H3 acetylation. No changes were observed in histone H3 occupancy or acetylation at viral IE gene promoters. Furthermore, p300 and CBP recruitment to IE gene promoters was not affected by the presence of curcumin. Finally, disruption of p300 expression using a short hairpin RNA did not affect viral IE gene expression. These results suggest that curcumin affects VP16-mediated recruitment of RNA polymerase II to IE gene promoters by a mechanism independent of p300/CBP histone acetyltransferase activity.
Kutluay
Sebla B
SB
Graduate Program in Cell and Molecular Biology, Michigan State University, East Lansing, MI 48824, USA.
Doroghazi
James
J
Roemer
Martha E
ME
Triezenberg
Steven J
SJ
D021581:Active Transport, Cell Nucleus; D000818:Animals; D001483:Base Sequence; D002522:Chlorocebus aethiops; D047369:Chromatin Immunoprecipitation; D003474:Curcumin / Q000494:pharmacology*; D017931:DNA Primers / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D017781:Genes, Immediate-Early / Q000187:drug effects*; D005814:Genes, Viral / Q000187:drug effects; D016679:Genome, Viral; D006367:HeLa Cells; D017405:Herpes Simplex Virus Protein Vmw65 / Q000378:metabolism; D018259:Herpesvirus 1, Human / Q000187:drug effects* / Q000235:genetics* / Q000472:pathogenicity / Q000502:physiology; D006801:Humans; D016366:Open Reading Frames; D010957:Plasmids / Q000235:genetics; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D012319:RNA Polymerase II / Q000378:metabolism; D014162:Transfection; D014709:Vero Cells; D010948:Viral Plaque Assay; D014774:Virulence / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects; D050880:p300-CBP Transcription Factors / Q000378:metabolism*
D017931:DNA Primers; D017405:Herpes Simplex Virus Protein Vmw65; D050880:p300-CBP Transcription Factors; D012319:RNA Polymerase II; D003474:Curcumin