Circadian control of hepatitis B virus replication

• DOI: 10.1038/s41467-021-21821-0
• Publication Date: 2021-03-12T11:07:02Z
• Authors: Xiaodong Zhuang; Donall Forde; Senko Tsukuda; Valentina D’Arienzo; Laurent Mailly; James M. Harris; Peter A. C. Wing; Helene Borrmann; Mirjam Schilling; Andrea Magri; Claudia Orbegozo ...; Robert J. Maidstone; Mudassar Iqbal; Miguel Garzon; Rosalba Minisini; Mario Pirisi; Sam Butterworth; Peter Balfe; David W. Ray; Koichi Watashi; Thomas F. Baumert; Jane A. McKeating
• Keywords: cccDNA

Abstract Chronic hepatitis B virus (HBV) infection is a major cause of liver disease and cancer worldwide for which there are no curative therapies. The challenge in curing eradicating or silencing the covalent closed circular DNA (cccDNA) form viral genome. circadian factors BMAL1/CLOCK REV-ERB master regulators transcriptome yet their role HBV replication unknown. We establish cycling cell-model demonstrate that directly regulates NTCP-dependent delta particle entry. Importantly, we show pharmacological activation inhibits vitro human chimeric mice. uncover BMAL1 to bind genomes increase promoter activity. Pharmacological inhibition through ligands reduces pre-genomic RNA de novo secretion. presence conserved E-box motifs among members Hepadnaviridae family highlight an evolutionarily regulating this small viruses.