Title |
Inhibitory effects of piceatannol on human cytomegalovirus (hCMV) in vitro |
Author |
San-Ying Wang1, Jing Zhang1, Xiao-Gang Xu1, Hui-Li Su1, Wen-Min Xing1, Zhong-Shan Zhang2,3, Wei-Hua Jin4, Ji-Huan Dai1, Ya-Zhen Wang1, Xin-Yue He4, Chuan Sun1, Jing Yan1*, and Gen-Xiang Mao1* |
Address |
1Zhejiang Provincial Key Lab of Geriatrics & Geriatrics Institute of Zhejiang Province, Department of Geriatrics, Zhejiang Hospital, Hangzhou 310030, P. R. China, 2Key Laboratory of Vector Biology and Pathogen Control of Zhejiang Province, Huzhou University, Huzhou 313000, P. R. China, 3Huzhou Central Hospital, Huzhou University, Huzhou 313000, P. R. China, 4College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310014, P. R. China |
Bibliography |
Journal of Microbiology, 58(8),716–723, 2020,
|
DOI |
10.1007/s12275-020-9528-2
|
Key Words |
piceatannol, hCMV, cellular senescence, p16INK4a,
ROS |
Abstract |
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 antihCMV
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. |