Department of Microbiology & Immunology Seminar: “Hepatitis B Virus Precore/Core Proteins: From Biology to Applications”

Title: “Hepatitis B Virus Precore/Core Proteins: From Biology to Applications”

Speaker:
Dr. Xupeng Hong
Postdoctoral Fellow, Dr. Charles Rice’s Group, Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY

Abstract:
Hepatitis B virus (HBV) is a hepatotropic DNA virus that chronically infects approximately 300 million individuals worldwide. Among the HBV-encoded proteins, the HBV core protein (HBc) plays a critical role in the HBV lifecycle. In contrast, the HBV precore protein, which shares the same sequence as HBc but also contains a unique N-terminal extension, is not essential for the HBV lifecycle but is thought to facilitate chronic HBV infection. We comprehensively characterized extracellular and intracellular HBV precore gene products in HBV-infected human hepatocytes as well as human hepatoma cells overexpressing the HBV precore protein. We found that, in addition to the classical HBV e antigen (HBeAg), the precore-related antigen, PreC, retaining the N-terminal signal peptide, was secreted in cell culture supernatant. We also detected the cytosolic precore precursor (p25) and intermediate (p22), in HBV-infected hepatocytes, which negatively regulated HBc expression and virion secretion. In addition, the cytosolic precore protein derivatives could assemble chimeric capsids with HBc, which were subsequently secreted in virions. Moreover, we characterized the HBV precore/core-related antigens and investigated their applications in patients and animal models as surrogate markers for intrahepatic viral activities. This allowed us to uncover mechanisms of viral clearance during the resolution of natural infection and after antiviral therapies. Altogether, our study has expanded our knowledge of the roles of HBV precore and core proteins in the HBV life cycle and provides a promising biomarker for monitoring intrahepatic viral levels and activities.