AUTHOR=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 

TITLE=Interferon-alpha responsible EPN3 regulates hepatitis B virus replication

JOURNAL=Frontiers in Medicine

VOLUME=Volume 9 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2022.944489

DOI=10.3389/fmed.2022.944489

ISSN=2296-858X

ABSTRACT=Hepatitis B virus (HBV) infection remains a major health problem worldwide, and the current antiviral therapy, including nucleoside analogues, 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 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 is the first to demonstrate the anti-HBV role of EPN3. The mechanism how it decreases HBV transcription is discussed.