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The Hepatitis B Virus Interactome: A Comprehensive Overview
Ellen Van Damme1, Jolien Vanhove1,2, Bryan Severyn3
1Janssen Research & Development, Janssen Pharmaceutical Companies, Beerse, Belgium.
Insights
Chronic hepatitis B (CHB) remains a global health challenge. This review details hepatitis B virus (HBV) host interactions, identifying novel therapeutic targets to achieve a functional cure for CHB.
Area of Science:
- Virology
- Hepatology
- Immunology
Background:
- Chronic hepatitis B (CHB) affects 292 million globally, with current treatments aiming for functional cure (HBsAg seroclearance and undetectable HBV-DNA).
- Functional cure is hindered by covalently closed circular DNA (cccDNA) and integrated HBV-DNA, with the role of HBsAg from integrated DNA unclear.
- Understanding HBV-host interactions is crucial for developing novel therapies targeting viral persistence.
Purpose of the Study:
- To provide a comprehensive review of the hepatitis B virus (HBV) host relationship.
- To identify novel therapeutic targets for achieving high rates of functional cure in CHB.
- To compile an interactome of HBV cccDNA, HBc, and HBx with host proteins.
Main Methods:
- Comprehensive literature review of HBV-host interactions from viral entry to release.
- Analysis of viral proteins and cccDNA interactions with the host proteome.
- Construction of an HBV interactome focusing on cccDNA, HBc, and HBx.
Main Results:
- Detailed exploration of the virus-host relationship throughout the HBV lifecycle.
- Identification of key viral proteins and cccDNA involved in maintaining HBV persistence and immune evasion.
- Compilation of a novel interactome for cccDNA, HBc, and HBx, highlighting previously unknown HBV-host protein interactions.
Conclusions:
- A deeper understanding of HBV-host interactions is essential for advancing CHB therapeutics.
- The identified interactome provides a valuable resource for pinpointing new targets to achieve functional cure.
- Further research into these interactions may lead to innovative strategies for HBV eradication.
Abstract:
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.
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