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

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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 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.

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Acknowledgments

This study was supported by the National Natural Science Foundation of China (81771520), funds from the Technology Department of Zhejiang Province (2016C34002), Zhejiang Provincial Natural Science Foundation (LQ20H250002), Chinese traditional medicine science and technology projects of Zhejiang Province (2018ZA004, 2018ZB002, and 2019- ZB005), the Health Bureau of Zhejiang Province (2019RC091 and 2020KY387), and Key Laboratory of Vector Biology and Pathogen Control of Zhejiang Province, Huzhou University (Grant No. HUZUL201904). Dr. Genxiang Mao is an Irma and Paul Milstein Program for Senior Health fellow supported by the MILSTEIN MEDICAL ASIAN AMERICAN Partnership Foundation (MMAAP Foundation) (http://www.mmaapf.org).

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Authors and Affiliations

  1. Zhejiang Provincial Key Lab of Geriatrics & Geriatrics Institute of Zhejiang Province, Department of Geriatrics, Zhejiang Hospital, Hangzhou, 310030, P. R. China

    San-Ying Wang, **g Zhang, **ao-Gang Xu, Hui-Li Su, Wen-Min **ng, Ji-Huan Dai, Ya-Zhen Wang, Chuan Sun, **g Yan & Gen-**ang Mao

  2. Key Laboratory of Vector Biology and Pathogen Control of Zhejiang Province, Huzhou University, Huzhou, 313000, P. R. China

    Zhong-Shan Zhang

  3. Huzhou Central Hospital, Huzhou University, Huzhou, 313000, P. R. China

    Zhong-Shan Zhang

  4. College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, 310014, P. R. China

    Wei-Hua ** & **n-Yue He

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  1. San-Ying Wang
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  2. **g Zhang
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  3. **ao-Gang Xu
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  13. Gen-**ang Mao
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Correspondence to **g Yan or Gen-**ang Mao.

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Wang, SY., Zhang, J., Xu, XG. et al. Inhibitory effects of piceatannol on human cytomegalovirus (hCMV) in vitro. J Microbiol. 58, 716–723 (2020). https://doi.org/10.1007/s12275-020-9528-2

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