Open AccessTargeting Hepatitis B Virus Covalently Closed Circular DNA and Hepatitis B Virus X Protein: Recent Advances and New Approaches
Author(s) -
Nicholas Adrian Prescott,
Yaron Bram,
Robert E. Schwartz,
Yael David
Publication year - 2019
Publication title -
acs infectious diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.324
H-Index - 39
ISSN - 2373-8227
DOI - 10.1021/acsinfecdis.9b00249
Subject(s) - cccdna , hbx , hepatitis b virus , minichromosome , biology , virology , circular dna , viral life cycle , virus , viral replication , dna virus , epigenetics , transcription (linguistics) , dna , computational biology , genetics , gene , genome , chromatin , linguistics , philosophy , hbsag
Chronic Hepatitis B virus (HBV) infection remains a worldwide concern and public health problem. Two key aspects of the HBV life cycle are essential for viral replication and thus the development of chronic infections: the establishment of the viral minichromosome, covalently closed circular (ccc) DNA, within the nucleus of infected hepatocytes and the expression of the regulatory Hepatitis B virus X protein (HBx). Interestingly, nuclear HBx redirects host epigenetic machinery to activate cccDNA transcription. In this Perspective, we provide an overview of recent advances in understanding the regulation of cccDNA and the mechanistic and functional roles of HBx. We also describe the progress toward targeting both cccDNA and HBx for therapeutic purposes. Finally, we outline standing questions in the field and propose complementary chemical biology approaches to address them.