IFNα subtype-specific susceptibility of HBV in the course of chronic infection

作者：Xiaohong Xie, Zehra Karakoese, Dilhumare Ablikim, Julia Ickler, Jonas Schuhenn, Xiaoqing Zeng, Xuemei Feng, Xuecheng Yang, Ulf Dittmer, Dongliang Yang, Kathrin Sutter, Jia Liu · 发表于：Frontiers in Immunology · 年份：2022 · DOI：10.3389/fimmu.2022.1017753 · 被引用次数：13 · 研究领域：Hepatitis B Virus Studies、Hepatitis C virus research、Hepatitis Viruses Studies and Epidemiology

Chronic hepatitis B virus (HBV) infection continues to be a major health problem worldwide and remains hard to be cured. Therapy with interferon (IFN) α is an important method for the clinical treatment of chronic hepatitis B. IFNα exhibits direct antiviral effects as well as immunomodulatory activities, which can induce sustained antiviral responses in part of the treated chronic hepatitis B patients. Numerous IFNα subtypes with high sequence identity between 76-96% exist which are characterized by diverse, non-redundant biological activities. Our previous studies have demonstrated that the clinically approved IFNα2 is not the most effective subtype for the anti-HBV treatment among all IFNα subtypes. So far very little is known about the IFNα subtype expression pattern during early HBV infection and the IFNα subtype-specific susceptibility during persistent HBV infection as well as its related cellular mechanism. Here we determined the Ifna subtype mRNA expression during acute and chronic HBV infection by using the well-established hydrodynamic injection (HDI) mouse model and we revealed a transient but strong expression of a panel of Ifna subtypes in the spleen of HBV persistent replication mice compared to HDI controls. Immunotherapy with distinct IFNα subtypes controlled chronic HBV infection. IFNα subtype-mediated antiviral response and immune activation were comprehensively analyzed in an AAV-HBV persistent infection murine model and murine IFNα2 was identified as the m...