The Hepatitis B Virus Nucleocapsid—Dynamic Compartment for Infectious Virus Production and New Antiviral Target

Hepatitis B virus (HBV) is a small enveloped DNA virus which replicates its tiny 3.2 kb genome by reverse transcription inside an icosahedral nucleocapsid, formed by a single ~180 amino acid capsid, or core, protein (Cp). HBV causes chronic hepatitis B (CHB), a severe liver disease responsible for n...

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Autores principales:	Matthias Niklasch, Peter Zimmermann, Michael Nassal
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	capsid capsid assembly capsid assembly modulator (CAM) capsid protein chronic hepatitis B (CHB) combination therapy Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/7f3e0cabf28d43529ad5e07dd05169c6
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spelling	oai:doaj.org-article:7f3e0cabf28d43529ad5e07dd05169c62021-11-25T16:49:11ZThe Hepatitis B Virus Nucleocapsid—Dynamic Compartment for Infectious Virus Production and New Antiviral Target10.3390/biomedicines91115772227-9059https://doaj.org/article/7f3e0cabf28d43529ad5e07dd05169c62021-10-01T00:00:00Zhttps://www.mdpi.com/2227-9059/9/11/1577https://doaj.org/toc/2227-9059Hepatitis B virus (HBV) is a small enveloped DNA virus which replicates its tiny 3.2 kb genome by reverse transcription inside an icosahedral nucleocapsid, formed by a single ~180 amino acid capsid, or core, protein (Cp). HBV causes chronic hepatitis B (CHB), a severe liver disease responsible for nearly a million deaths each year. Most of HBV’s only seven primary gene products are multifunctional. Though less obvious than for the multi-domain polymerase, P protein, this is equally crucial for Cp with its multiple roles in the viral life-cycle. Cp provides a stable genome container during extracellular phases, allows for directed intracellular genome transport and timely release from the capsid, and subsequent assembly of new nucleocapsids around P protein and the pregenomic (pg) RNA, forming a distinct compartment for reverse transcription. These opposing features are enabled by dynamic post-transcriptional modifications of Cp which result in dynamic structural alterations. Their perturbation by capsid assembly modulators (CAMs) is a promising new antiviral concept. CAMs inappropriately accelerate assembly and/or distort the capsid shell. We summarize the functional, biochemical, and structural dynamics of Cp, and discuss the therapeutic potential of CAMs based on clinical data. Presently, CAMs appear as a valuable addition but not a substitute for existing therapies. However, as part of rational combination therapies CAMs may bring the ambitious goal of a cure for CHB closer to reality.Matthias NiklaschPeter ZimmermannMichael NassalMDPI AGarticlecapsidcapsid assemblycapsid assembly modulator (CAM)capsid proteinchronic hepatitis B (CHB)combination therapyBiology (General)QH301-705.5ENBiomedicines, Vol 9, Iss 1577, p 1577 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	capsid capsid assembly capsid assembly modulator (CAM) capsid protein chronic hepatitis B (CHB) combination therapy Biology (General) QH301-705.5
spellingShingle	capsid capsid assembly capsid assembly modulator (CAM) capsid protein chronic hepatitis B (CHB) combination therapy Biology (General) QH301-705.5 Matthias Niklasch Peter Zimmermann Michael Nassal The Hepatitis B Virus Nucleocapsid—Dynamic Compartment for Infectious Virus Production and New Antiviral Target
description	Hepatitis B virus (HBV) is a small enveloped DNA virus which replicates its tiny 3.2 kb genome by reverse transcription inside an icosahedral nucleocapsid, formed by a single ~180 amino acid capsid, or core, protein (Cp). HBV causes chronic hepatitis B (CHB), a severe liver disease responsible for nearly a million deaths each year. Most of HBV’s only seven primary gene products are multifunctional. Though less obvious than for the multi-domain polymerase, P protein, this is equally crucial for Cp with its multiple roles in the viral life-cycle. Cp provides a stable genome container during extracellular phases, allows for directed intracellular genome transport and timely release from the capsid, and subsequent assembly of new nucleocapsids around P protein and the pregenomic (pg) RNA, forming a distinct compartment for reverse transcription. These opposing features are enabled by dynamic post-transcriptional modifications of Cp which result in dynamic structural alterations. Their perturbation by capsid assembly modulators (CAMs) is a promising new antiviral concept. CAMs inappropriately accelerate assembly and/or distort the capsid shell. We summarize the functional, biochemical, and structural dynamics of Cp, and discuss the therapeutic potential of CAMs based on clinical data. Presently, CAMs appear as a valuable addition but not a substitute for existing therapies. However, as part of rational combination therapies CAMs may bring the ambitious goal of a cure for CHB closer to reality.
format	article
author	Matthias Niklasch Peter Zimmermann Michael Nassal
author_facet	Matthias Niklasch Peter Zimmermann Michael Nassal
author_sort	Matthias Niklasch
title	The Hepatitis B Virus Nucleocapsid—Dynamic Compartment for Infectious Virus Production and New Antiviral Target
title_short	The Hepatitis B Virus Nucleocapsid—Dynamic Compartment for Infectious Virus Production and New Antiviral Target
title_full	The Hepatitis B Virus Nucleocapsid—Dynamic Compartment for Infectious Virus Production and New Antiviral Target
title_fullStr	The Hepatitis B Virus Nucleocapsid—Dynamic Compartment for Infectious Virus Production and New Antiviral Target
title_full_unstemmed	The Hepatitis B Virus Nucleocapsid—Dynamic Compartment for Infectious Virus Production and New Antiviral Target
title_sort	hepatitis b virus nucleocapsid—dynamic compartment for infectious virus production and new antiviral target
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/7f3e0cabf28d43529ad5e07dd05169c6
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The Hepatitis B Virus Nucleocapsid—Dynamic Compartment for Infectious Virus Production and New Antiviral Target

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