Requirement of CRTC1 coactivator for hepatitis B virus transcription

Tang, Hei-Man Vincent; Gao, Wei-Wei; Chan, Chi-Ping; Cheng, Yun; Chaudhary, Vidyanath; Deng, Jian-Jun; Yuen, Kit-San; Wong, Chun-Ming; Ng, Irene Oi-Lin; Kok, Kin-Hang; Zhou, Jie; Jin, Dong-Yan

HBV infects hepatocytes that express its receptor named sodium taurocholate cotransporting polypeptide (3) . Upon viral entry and release of genetic material, covalently closed circular DNA (cccDNA) is generated from relaxed circular DNA (rcDNA) and complexed with different viral proteins, histones, transcription factors and coactivators to form a nuclear minichromosome, which serves as a central template for all HBV transcription (4, 5) . Transcription of pregenomic RNA (pgRNA) from cccDNA is rate-limiting in genome amplification and replication. cccDNA can be amplified through an unknown mechanism (6) . The stability of the cccDNA pool is a major determinant in viral clearance. cccDNA is refractory to antivirals such as nucleoside or nucleotide analogs. cccDNA is also accounted for viral relapse after cessation of anti-HBV therapy (5) . cccDNA is therefore an important target for better control and elimination of HBV infection (7, 8) . In line with this, understanding the mechanism by which HBV transcription from cccDNA is regulated might reveal new strategies for therapeutic intervention.