Inhibitory effects of piceatannol on human cytomegalovirus (hCMV) in vitro.
Human cytomegalovirus (hCMV) is a ubiquitous herpesvirus, which results in the establishment of a latent infection that persists throughout the life of the host and can be reactivated when the immunity is low. Currently, there is no vaccine for hCMV infection, and the licensed antiviral drugs mainly target the viral enzymes and have obvious adverse reactions. Thus, it is important to search for compounds with anti-hCMV properties. The present study aimed to investigate the suppressive effects of piceatannol on hCMV Towne strain infection and the putative underlying mechanisms using human diploid fibroblast WI-38 cells. Piceatannol supplementation prevented the lytic changes induced by hCMV infection in WI-38 cells. Furthermore, piceatannol suppressed the expression of hCMV immediate-early (IE) and early (E) proteins as well as the replication of hCMV DNA in a dose-dependent manner. Moreover, hCMV-induced cellular senescence was suppressed by piceatannol, as shown by a decline in the senescence-associated β-galactosidase (SA-β-Gal) activity and decreased production of intracellular reactive oxygen species (ROS). p16INK4a, a major senescence-associated molecule, was dramatically elevated by current hCMV infection that was attenuated by pre-incubation with piceatannol in a dose-dependent manner. These results demonstrated that piceatannol suppressed the hCMV infection via inhibition of the activation of p16INK4a and cellular senescence induced by hCMV. Together, these findings indicate piceatannol as a novel and potent anti-hCMV agent with the potential to be developed as an effective treatment for chronic hCMV infection.
['Wang|San-Ying|SY|', 'Zhang|Jing|J|', 'Xu|Xiao-Gang|XG|', 'Su|Hui-Li|HL|', 'Xing|Wen-Min|WM|', 'Zhang|Zhong-Shan|ZS|', 'Jin|Wei-Hua|WH|', 'Dai|Ji-Huan|JH|', 'Wang|Ya-Zhen|YZ|', 'He|Xin-Yue|XY|', 'Sun|Chuan|C|', 'Yan|Jing|J|', 'Mao|Gen-Xiang|GX|']
D000998:Antiviral Agents D002460:Cell Line D016922:Cellular Senescence D019941:Cyclin-Dependent Kinase Inhibitor p16 D003587:Cytomegalovirus D003586:Cytomegalovirus Infections D058492:Drug Repositioning D006801:Humans D017874:Immediate-Early Proteins D017382:Reactive Oxygen Species D013267:Stilbenes D014779:Virus Replication D001616:beta-Galactosidase
piceatannol hCMV cellular senescence ROS p16INK4a