Li Xueqian, Wang Zhe, Zhou Weiping, Fu Xuanhe, Zhang Yunpeng, Sun Ye, Yang Biao, Bai Yuxin, Dai Chunwei, Xu Xiaolun, Cui Fan, Zhao Ying, Zhang Yuping, Wang Bengang, Li Yingfang, Muramatsu Masamichi, Wakae Kousho, Liu Guangyan
Department of Pathogen Biology, Shenyang Medical College, Shenyang, China.
Department of Medical Oncology, Affiliated Zhongshan Hospital of Dalian University, Dalian, China.
Front Med (Lausanne). 2022 Jul 22;9:944489. doi: 10.3389/fmed.2022.944489. eCollection 2022.
Hepatitis B virus (HBV) infection remains a major health problem worldwide, and the current antiviral therapy, including nucleoside analogs, cannot achieve life-long cure, and clarification of antiviral host immunity is necessary for eradication. Here, we found that a clathrin-binding membrane protein epsin3 (EPN3) negatively regulates the expression of HBV RNA. EPN3 expression was induced by transfection of an HBV replicon plasmid, and reduced HBV-RNA level in hepatic cell lines and murine livers hydrodynamically injected with the HBV replicon plasmid. Viral RNA reduction by EPN3 was dependent on transcription, and independent from epsilon structure of viral RNA. Viral RNA reduction by overexpression of p53 or IFN-α treatment, was attenuated by knockdown of EPN3, suggesting its role downstream of IFN-α and p53. Taken together, this study demonstrates the anti-HBV role of EPN3. The mechanism how it decreases HBV transcription is discussed.
乙型肝炎病毒（HBV）感染仍是全球主要的健康问题，目前包括核苷类似物在内的抗病毒疗法无法实现终身治愈，阐明抗病毒宿主免疫对于根除HBV至关重要。在此，我们发现一种网格蛋白结合膜蛋白Epsin3（EPN3）对HBV RNA的表达具有负调控作用。通过转染HBV复制子质粒可诱导EPN3表达，并且在肝细胞系以及经流体动力学注射HBV复制子质粒的小鼠肝脏中，EPN3可降低HBV RNA水平。EPN3介导的病毒RNA减少依赖于转录，且与病毒RNA的ε结构无关。p53过表达或IFN-α处理所导致的病毒RNA减少，会因EPN3的敲低而减弱，提示EPN3在IFN-α和p53的下游发挥作用。综上所述，本研究证明了EPN3的抗HBV作用。文中还讨论了其降低HBV转录的机制。
