Table_2_Interferon-alpha responsible EPN3 regulates hepatitis B virus replication.docx

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（Hepatitis B virus, HBV）感染仍是全球范围内的重大公共卫生问题，当前包括核苷类似物在内的抗病毒治疗方案均无法实现终身治愈，阐明抗病毒宿主免疫机制是实现病毒根除的必要前提。本研究发现，网格蛋白结合膜蛋白epsin3（EPN3）可负调控HBV RNA的表达。转染HBV复制子质粒可诱导EPN3的表达，并可在肝细胞系及经水动力转染导入HBV复制子质粒的小鼠肝脏中降低HBV RNA水平。EPN3介导的病毒RNA水平降低依赖于转录过程，且与病毒RNA的ε结构无关。过表达p53或经干扰素α（IFN-α）处理所介导的病毒RNA水平降低，可因EPN3敲低而被削弱，提示EPN3作用于IFN-α与p53通路的下游。综上，本研究证实了EPN3的抗HBV作用，并对其降低HBV转录的分子机制进行了探讨。