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Inhibitory effects of piceatannol on human cytomegalovirus (hCMV) in vitro.
Journal of Microbiology ( IF 3 ) Pub Date : 2020-06-10 , DOI: 10.1007/s12275-020-9528-2
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
Affiliation  

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.

中文翻译:

皮卡替诺醇在体外对人巨细胞病毒(hCMV)的抑制作用。

人巨细胞病毒(hCMV)是一种普遍存在的疱疹病毒,可导致潜伏感染的建立,这种潜伏感染会在宿主的整个生命周期中持续存在,并且在免疫力低下时可以重新激活。当前,没有用于hCMV感染的疫苗,并且许可的抗病毒药物主要靶向病毒酶,并且具有明显的不良反应。因此,重要的是寻找具有抗hCMV特性的化合物。本研究的目的是调查使用人二倍体成纤维细胞WI-38细胞对皮卡替诺醇对hCMV Towne株感染的抑制作用及其可能的潜在机制。皮卡坦酚的补充可防止WI-38细胞中hCMV感染引起的裂解改变。此外,Piceatannol以剂量依赖性方式抑制了hCMV即早(IE)和早期(E)蛋白的表达以及hCMV DNA的复制。此外,如通过衰老相关的β-半乳糖苷酶(SA-β-Gal)活性下降和细胞内活性氧种类(ROS)的减少所表明,皮卡替诺醇抑制了hCMV诱导的细胞衰老。16INK4a,一种主要的衰老相关分子,由于目前的hCMV感染而显着升高,而该作用因与皮甲三醇预先温育以剂量依赖的方式而减弱。这些结果表明,皮卡替诺醇通过抑制p16 INK4a的活化和hCMV诱导的细胞衰老来抑制hCMV感染。总之,这些发现表明,皮卡季诺醇是一种新型且有效的抗hCMV药物,有望被开发为对慢性hCMV感染的有效治疗方法。
更新日期:2020-06-10
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