Despite the availability of a prophylactic vaccine, chronic hepatitis B (CHB) caused by the hepatitis B virus (HBV) is a major health problem affecting an estimated 292 million people globally. Current therapeutic goals are to achieve functional cure characterized by HBsAg seroclearance and the absence of HBV-DNA after treatment cessation. However, at present, functional cure is thought to be complicated due to the presence of covalently closed circular DNA (cccDNA) and integrated HBV-DNA. Even if the episomal cccDNA is silenced or eliminated, it remains unclear how important the high level of HBsAg that is expressed from integrated HBV DNA is for the pathology. To identify therapies that could bring about high rates of functional cure, in-depth knowledge of the virus’ biology is imperative to pinpoint mechanisms for novel therapeutic targets. The viral proteins and the episomal cccDNA are considered integral for the control and maintenance of the HBV life cycle and through direct interaction with the host proteome they help create the most optimal environment for the virus whilst avoiding immune detection. New HBV-host protein interactions are continuously being identified. Unfortunately, a compendium of the most recent information is lacking and an interactome is unavailable. This article provides a comprehensive review of the virus-host relationship from viral entry to release, as well as an interactome of cccDNA, HBc, and HBx.

尽管有预防性疫苗可用，但由乙型肝炎病毒 (HBV) 引起的慢性乙型肝炎 (CHB) 是一个主要的健康问题，影响全球约 2.92 亿人。目前的治疗目标是实现以 HBsAg 血清清除和治疗停止后 HBV-DNA 缺失为特征的功能性治愈。然而，目前，由于共价闭合环状 DNA (cccDNA) 和整合的 HBV-DNA 的存在，功能性治愈被认为是复杂的。即使附加型 cccDNA 被沉默或消除，仍不清楚从整合的 HBV DNA 中表达的高水平 HBsAg 对病理学的重要性。为了确定可以带来高功能治愈率的疗法，必须深入了解病毒的生物学知识，以确定新治疗靶点的机制。病毒蛋白和附加型 cccDNA 被认为是控制和维持 HBV 生命周期不可或缺的一部分，通过与宿主蛋白质组的直接相互作用，它们有助于为病毒创造最佳环境，同时避免免疫检测。新的HBV-宿主蛋白相互作用不断被发现。不幸的是，缺乏最新信息的概要，并且无法获得交互组。本文全面回顾了从病毒进入到释放的病毒-宿主关系，以及 cccDNA、HBc 和 HBx 的相互作用组。