TY - JOUR
T1 - Curcumin inhibits herpes simplex virus immediate-early gene expression by a mechanism independent of p300/CBP histone acetyltransferase activity
AU - Kutluay, Sebla B.
AU - Doroghazi, James
AU - Roemer, Martha E.
AU - Triezenberg, Steven J.
N1 - Funding Information:
This work was supported by the Department of Biochemistry and Molecular Biology at Michigan State University and by the Van Andel Research Institute. SK was supported by a special fellowship from the College of Natural Science at Michigan State University and by a predoctoral fellowship from the American Heart Association. JD was supported in part by summer undergraduate research fellowships from the American Society for Microbiology. We thank Dan Ducat and Dr. Franciso Herrera for preparing the pSUPER-p300 construct. We also thank Dr. Eric Xu, Dr. Xu Lu, and Dr. Francisco Herrera for thoughtful comments on the manuscript.
PY - 2008/4/10
Y1 - 2008/4/10
N2 - 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.
AB - 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.
KW - Chromatin
KW - Coactivator
KW - Curcumin
KW - Lytic infection
KW - Transcriptional activation
KW - VP16
UR - http://www.scopus.com/inward/record.url?scp=40849139195&partnerID=8YFLogxK
U2 - 10.1016/j.virol.2007.11.028
DO - 10.1016/j.virol.2007.11.028
M3 - Article
C2 - 18191976
AN - SCOPUS:40849139195
SN - 0042-6822
VL - 373
SP - 239
EP - 247
JO - Virology
JF - Virology
IS - 2
ER -