家蝇抗菌肽cecropin抗HBV作用及其机制研究

Musca domestica antibacterial peptide cecropin (MDC) is a kind of antibacterial peptides from Musca domestica larvae found by our research group. In the antibacterial mechanism study, we found that the bacteria cell membrane can destroy by MDC, and intracellular DNA may also be its target. Then, MDC maybe have effect on the hepatitis B virus (HBV), which is a DNA virus containing outer membrane. In the previous study, we found that MDC has significant anti-HBV activity in vitro. But the anti-HBV activity of MDC in vivo and the mechanism of anti-HBV effect is not clear. This project intends to investigate anti-HBV activity of MDC in vivo and the mechanism of anti-HBV effect using HBV transgenic mice and HepaRG cells. According to the key events in the process of HBV infect hepatocytes, we design the experiment aiming at different potential targets. We intend to find the effect of targets of Musca domestica antibacterial peptide cecropin against HBV. The main research contents of the project include: 1. Investigate in vivo anti-HBV activity of MDC through animal experiment; 2. Investigate the mechanism of anti-HBV effect by study the influence of MDC against the virus particles, host cells and the HBV life cycle including adhesion, entry, replication, assembly and release. If we can achieve the desired results, we will provide a new drug candidate molecules for the development of anti-HBV drugs, and we will also expand the field of research for the multi-function study of active molecules from insect.

家蝇抗菌肽cecropin（MDC）是本课题组从家蝇幼虫体内发现的一种昆虫抗菌肽，我们在抗菌机制研究中发现其可破坏细菌的细胞膜，且胞内DNA也可能是其作用靶点，那么它对乙型肝炎病毒(HBV)这种含有包膜的DNA病毒作用效果又如何呢？我们前期研究发现MDC具有显著体外抗HBV活性，但其体内抗HBV作用及机制不明确。本项目拟以HBV转基因小鼠和HepaRG细胞为实验对象，在进一步确证MDC抗HBV活性的基础上，根据HBV感染细胞的关键事件，通过针对不同潜在靶点的实验设计，寻找家蝇抗菌肽cecropin作用靶点。主要研究内容包括:①通过动物实验，研究其体内抗HBV效果；②通过研究其对病毒、宿主细胞和HBV生命周期中黏附、进入、生物合成、装配、释放等过程及其关键分子的影响，阐明其抗HBV作用机制。如能取得预期效果，将为抗HBV药物的研发提供新的候选分子，也将为昆虫来源活性分子的多功能研究拓展视野。

乙型肝炎病毒（hepatitis B virus, HBV）持续感染会导致急慢性乙型肝炎，并可能发展成肝硬化和肝癌，目前临床尚无根治乙肝的特效药物。抗菌肽具有显著抗菌、抗肿瘤、免疫调节活性，毒副作用小，应用开发前景良好。家蝇抗菌肽cecropin（MDC）是本课题组从家蝇幼虫体内发现的一种昆虫抗菌肽，我们近期研究显示家蝇抗菌肽cecropin具有显著体外抗HBV活性，但其体内抗HBV作用及机制尚不明确。本项目首先以HBV转基因小鼠为模型，明确了家蝇抗菌肽cecropin体内抗HBV作用，在此基础上，通过研究其对病毒、宿主细胞和HBV生命周期中黏附、进入、生物合成、装配、释放等过程及其关键分子的影响，初步阐明其抗HBV作用机制。项目实施有望为抗HBV药物的研发提供新的候选分子，也为昆虫来源活性分子的多功能研究拓展了视野。