Mechanism of Hepatitis B Virus cccDNA Formation.

TitleMechanism of Hepatitis B Virus cccDNA Formation.
Publication TypeJournal Article
Year of Publication2021
AuthorsWei, L, Ploss, A
JournalViruses
Volume13
Issue8
Date Published2021/07/27
ISSN1999-4915
Abstract

Hepatitis B virus (HBV) remains a major medical problem affecting at least 257 million chronically infected patients who are at risk of developing serious, frequently fatal liver diseases. HBV is a small, partially double-stranded DNA virus that goes through an intricate replication cycle in its native cellular environment: human hepatocytes. A critical step in the viral life-cycle is the conversion of relaxed circular DNA (rcDNA) into covalently closed circular DNA (cccDNA), the latter being the major template for HBV gene transcription. For this conversion, HBV relies on multiple host factors, as enzymes capable of catalyzing the relevant reactions are not encoded in the viral genome. Combinations of genetic and biochemical approaches have produced findings that provide a more holistic picture of the complex mechanism of HBV cccDNA formation. Here, we review some of these studies that have helped to provide a comprehensive picture of rcDNA to cccDNA conversion. Mechanistic insights into this critical step for HBV persistence hold the key for devising new therapies that will lead not only to viral suppression but to a cure.

DOI10.3390/v13081463
Alternate JournalViruses
PubMed ID34452329
PubMed Central IDPMC8402782
Grant ListR01 AI138797 / AI / NIAID NIH HHS / United States
R01AI107301 / / National Institute of Allergy and Infectious Diseases /
R01AI146917 / / National Institute of Allergy and Infectious Diseases /
R01AI153236 / / National Institute of Allergy and Infectious Diseases /
RSG-15-048-01-MPC / / American Cancer Society /
101539 / / Burroughs Wellcome Fund /
W81XWH1810237 / / U.S. Department of Defense /
DFHS17PPC011 / / New Jersey Commission on Cancer Research /