HBV Replication Cycle subviral particles receptor(s) entry Cytoplasm secretion secretion endocytosis Golgi IVB M cccDNA formation intracellular CCcDNA ampl CCCDNA minichromosor NA synthesis 2,4kb A transcription 2.1kb A 5kb translation 3.5kb pregenomic RNA Nucleus encapsidation core A structure t of hBv vi 2. Encapsidate viral pol/ pgRNA complex and host subsequent DNA replication and rcDNA deproteinati Deliver rcDNA/DP-rCDNA into nucleus for CccDNA formation 4. A putative nucleosome- interacting protein in CCcDNA minichromosome
HBV Replication Cycle 1. A structure component of HBV virion. 2. Encapsidate viral pol/pgRNA complex and host subsequent DNA replication and rcDNA deproteination. 3. Deliver rcDNA/DP-rcDNA into nucleus for cccDNA formation. 4. A putative nucleosome-interacting protein in cccDNA minichromosome
Hepatitis B virus life cycle ntry of HBV Core particle mint into cel I strand synthesis Vesicular transport Core particle RNA packaging CCCDNA Image courtesy of The New England Journal of
Hepatitis B Virus life cycle Image courtesy of The New England Journal of Medicine
HBV replication Approved antiviral drugs only inhibit Entry replication CCCDNA persists in hepatocyte nuclei even during drug therapy Uncoating XocytosIS cccDNa degradation or inactivation could eliminate HBV persistence adding into ER Nuclear HBSA mport Recycling Reverse HBcAg/Polymera inscription DNA Targeted Viral proteins Endonuclease RT epair nearization and 上 encapsidation degradation pgRN anscriptidTal CCCDNA Translatio CYTOPLASM NUCLEUS Mutation/inactivation Weber, et al. Mol Ther 2013
• Approved antiviral drugs only inhibit replication HBV replication Uncoating Nuclear import Repair cccDNA rcDNA Transcription Translation Encapsidation Viral proteins Budding into ER Exocytosis Entry CYTOPLASM NUCLEUS Viral RNAs RTi Reverse Transcription Targeted Endonuclease HBcAg/Polymerase HBsAg Recycling pgRNA • cccDNA degradation or inactivation could eliminate HBV persistence Linearization and degradation • cccDNA persists in hepatocyte nuclei even during drug therapy Mutation/inactivation Weber, et al, Mol Ther 2013
Hepatitis B Virus-Replication Viral entry Nucleus
Hepatitis B Virus - Replication Viral entry Nucleus
Hepatitis B Virus-Replication Viral entry 8O Uncoating Nuclear import CCCDNA Repair Transcription n 5 33 2.4/21 kb RNA 3.5 kb rna
Uncoatin g Nuclear import Repair Transcriptio n cccDNA 5’ 5’ 3’ 3’ 3.5 kb RNA Viral entry 2.4/2.1 kb RNA Hepatitis B Virus - Replication