Department of Microbiology & Immunology Seminar Series: “HBV Capsid: Core In Virus Entry and Persistence”
Title: “HBV Capsid: Core In Virus Entry and Persistence”
Speaker: Jianming Hu, MD, PhD
Professor, Department of Microbiology and Immunology
Penn State University College of Medicine
Location: Med-Dent NE301 or via Zoom
Abstract:
Hepatitis B virus (HBV) relies on the core protein (HBc) to establish productive infection, as defined by the formation of the covalently closed circularized DNA (cccDNA), as well as to carry out almost every step of the lifecycle following cccDNA formation. Multiple copies of HBc form an icosahedral capsid shell that encapsidates the viral pregenomic RNA (pgRNA) and facilitates the reverse transcription of pgRNA to a relaxed circular DNA (rcDNA) within the capsid. During infection, the complete HBV virion, which contains an outer envelope layer in addition to the internal nucleocapsid containing rcDNA, enters human hepatocytes via endocytosis and traffics through the cytoplasm to deliver its rcDNA to the nucleus to produce cccDNA. In addition, progeny rcDNA, newly formed in cytoplasmic nucleocapsids, is also delivered to the nucleus in the same cell to form more cccDNA in a process called intracellular cccDNA amplification or recycling. As cccDNA is the molecular basis of HBV infection and persistence, its elimination is the holy grail in the ongoing pursuit of an HBV cure.
I will focus on our recent work demonstrating differential effects of HBc in affecting cccDNA formation during de novo infection vs. recycling. These results implicate a critical role of HBc in determining HBV trafficking during infection, as well as in nucleocapsid disassembly (uncoating) to release rcDNA, events essential for cccDNA formation. Our work also suggests that HBc likely functions in these processes via interactions with host factors, which contributes critically to HBV host tropism. A better understanding of the roles of HBc in HBV entry, cccDNA formation, and host species tropism should accelerate ongoing efforts to target HBc and cccDNA for the development of an HBV cure and facilitate the establishment of convenient animal models for both basic research and drug development.