Effects of Resveratrol on Hepatitis B Virus Replication: In vitro and in vivo Experiments.

IF 3.2 4区医学 Q3 VIROLOGY

Intervirology Pub Date : 2022-01-01 Epub Date: 2022-09-09 DOI:10.1159/000525807

Peipei Pan, Jiaohui Li, Wei Lin, Guangyan Long

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引用次数: 2

Abstract

Introduction: Hepatitis B virus (HBV) infection is a disease with high incidence and lack of effective treatment. In this study, we further explored the mechanism of resveratrol (RVT) in the inhibition of HBV replication. The effects of RVT on HBV replication were verified using in vitro and in vivo experiments.

Methods: HepG2 and HepG2.2.15 cell lines were cultured in vitro, and different concentrations of RVT were used to determine its effect on the proliferation of the two cell lines. Autophagy agonists and inhibitors were given, and whether RVT exerts its effect on the proliferation of HepG2 and HepG2.2.15 cells through autophagy was determined. Reverse transcription-quantitative polymerase chain reaction and Western blot were used to detect changes in autophagy-related factors LC3-II, LC3-I, Beclin 1, and p62. Through transfection of pmiR-155, shmiR-155, and the corresponding control group, the relevant mechanism of RVT in inhibiting the proliferation of HepG2 and HepG2.2.15 cells was analyzed. RVT inhibited the toxicity for HepG2.2.15 cells and reduced HBV replication in vitro (p < 0.05). This effect of RVT was enhanced by rapamycin (RAPA; autophagy activator; p < 0.05) but was partially reversed by 3-MA (autophagy inhibitor; p < 0.05). In addition, our results showed that miR-155 expression was higher in HepG2.2.15 cells than in HepG cells (p < 0.05). miR-155 expression in the RVT treatment group was significantly reduced (p < 0.05). We designed an miR-155 overexpression plasmid, low miR-155 expression plasmid, and the corresponding negative control for transfection and found that transfection of pmiR-155 can partially reverse the effect of RVT (p < 0.05), while transfection with shmiR-155 can enhance the effect of RVT (p < 0.05).

Discussion: RVT inhibits miR-155, activates autophagy, inhibits the toxicity for HepG2.2.15 cells, and reduces HBV replication, providing a new research direction for the treatment of HBV infection.

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白藜芦醇对乙型肝炎病毒复制的影响:体外和体内实验。

乙型肝炎病毒(HBV)感染是一种高发且缺乏有效治疗的疾病。在本研究中，我们进一步探讨了白藜芦醇(RVT)抑制HBV复制的机制。通过体外和体内实验验证了RVT对HBV复制的影响。方法:体外培养HepG2和HepG2.2.15细胞系，采用不同浓度RVT测定其对两种细胞系增殖的影响。给予自噬激动剂和自噬抑制剂，观察RVT是否通过自噬作用影响HepG2和HepG2.2.15细胞的增殖。采用逆转录-定量聚合酶链反应和Western blot检测自噬相关因子LC3-II、LC3-I、Beclin 1和p62的变化。通过转染pmiR-155、shmiR-155及相应的对照组，分析RVT抑制HepG2、HepG2.2.15细胞增殖的相关机制。RVT抑制HepG2.2.15细胞毒性，降低HBV体外复制(p < 0.05)。雷帕霉素(RAPA;自噬激活;p < 0.05)，但被3-MA(自噬抑制剂)部分逆转;P < 0.05)。此外，我们的研究结果显示，miR-155在HepG2.2.15细胞中的表达高于HepG细胞(p < 0.05)。RVT治疗组miR-155表达明显降低(p < 0.05)。我们设计了miR-155过表达质粒、miR-155低表达质粒和相应的阴性对照进行转染，发现转染pmiR-155可以部分逆转RVT的作用(p < 0.05)，而转染shmiR-155可以增强RVT的作用(p < 0.05)。讨论:RVT抑制miR-155，激活自噬，抑制对HepG2.2.15细胞的毒性，减少HBV复制，为治疗HBV感染提供了新的研究方向。

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来源期刊

Intervirology 医学-病毒学

CiteScore

5.40

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： ''Intervirology'' covers progress in both basic and clinical virus research, and aims to provide a forum for the various disciplines within virology. Issues publishing original papers alternate with thematic issues, focusing on clearly defined topics. This thematic concentration serves to make timely reviews, research reports and controversy easily accessible to both specialists in the field and those who want to keep track of the latest developments outside their own area of interest. In addition to original papers, regular issues publish short communications and letters to the editor to provide readers with a forum for the exchange of ideas and comments. The scope encompasses work on the molecular biology of human and animal viruses, including genome organization and regulation, and the structure and function of viral proteins. The pathogenesis, immunology, diagnosis, epidemiology, prophylaxis and therapy of viral diseases are considered.