Structure and Molecular Virology
Souphalone Luangsay
Lyon University, Cancer Research Center of Lyon (CRCL), INSERM, Lyon, France
Search for more papers by this authorSouphalone Luangsay
Lyon University, Cancer Research Center of Lyon (CRCL), INSERM, Lyon, France
Search for more papers by this authorHoward C. Thomas BSc, PhD, FRCP, FRCPath, FMedSci
Emeritus Professor of Hepatology, Department of Medicine, Imperial College London, London, UK
Search for more papers by this authorAnna S.F. Lok MD
Alice Lohrman Andrews Research Professor in Hepatology, Director of Clinical Hepatology, Professor of Internal Medicine, Associate Chair for Clinical Research, Department of Internal Medicine, University of Michigan Health System, Ann Arbor, MI, USA
Search for more papers by this authorStephen A. Locarnini MBBS, BSc(Hons), PhD, FRCPath
Head, Research & Molecular Development, Victorian Infectious Diseases Reference Laboratory, Melbourne, VIC, Australia
Search for more papers by this authorArie J. Zuckerman MD, DSc, FRCP, FRCPath, FMedSci
Emeritus Professor of Medical Microbiology, Formerly Principal and Dean, Royal Free Hospital School of Medicine
Search for more papers by this authorSummary
The hepatitis B virus displays a unique infectious cycle sharing similar features to retroviruses. Infectious virions contain relaxed circular DNA (rcDNA), which is delivered to the nucleus before the initiation of replication. Viral DNA integration into host cellular chromosome is not mandatory for virus replication. Instead, a covalently closed circular DNA (cccDNA) is generated from incoming rcDNA and serves as the template for the transcription of viral RNAs. The epigenetic control of the transcriptional activity of cccDNA by the HBx protein or cytokines may influence HBV replication and pathogenesis. In the cytoplasm, viral genome replication occurs within nucleocapsids and involves a protein-primed reverse transcription of the pregenomic RNA into viral minus-strand DNA, followed by DNA-dependent DNA synthesis to generate new rcDNA. Nucleocapsids can be recycled back to the nucleus to amplify or maintain the pool of cccDNA, or be directed to the endoplasmic reticulum to be packaged by envelope proteins and secreted as infectious viruses.
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