Inhibitory effects of piceatannol on human cytomegalovirus (hCMV) in vitro

San-Ying Wang; Jing Zhang; Xiao-Gang Xu; Hui-Li Su; Wen-Min Xing; Zhong-Shan Zhang; Wei-Hua Jin; Ji-Huan Dai; Ya-Zhen Wang; Xin-Yue He; Chuan Sun; Jing Yan; Gen-Xiang Mao

doi:10.1007/s12275-020-9528-2

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Inhibitory effects of piceatannol on human cytomegalovirus (hCMV) in vitro: San-Ying Wang ¹, Jing Zhang ¹, Xiao-Gang Xu ¹, Hui-Li Su ¹, Wen-Min Xing ¹, Zhong-Shan Zhang ^2,3, Wei-Hua Jin ⁴, Ji-Huan Dai ¹, Ya-Zhen Wang ¹, Xin-Yue He ⁴, Chuan Sun ¹, Jing Yan ¹, Gen-Xiang Mao ¹; Journal of Microbiology 2020;58(8):716-723.
DOI: https://doi.org/10.1007/s12275-020-9528-2
Published online: June 10, 2020

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. China¹Zhejiang 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

Corresponding author: Jing Yan , Tel: +86-571-8737-7772,
Gen-Xiang Mao , Tel: +86-571-8737-7772,

Received: 5 November 2019 • Revised: 20 April 2020 • Accepted: 6 May 2020

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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.

Keywords: microbial interaction;microbiome;omics;source tracking;viral ecology

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Inhibitory effects of piceatannol on human cytomegalovirus (hCMV) in vitro

J. Microbiol. 2020;58(8):716-723. Published online June 10, 2020

DOI: https://doi.org/10.1007/s12275-020-9528-2

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