Liver cancer is a significant health concern associated with viral hepatitis, particularly hepatitis virus type B (HBV) and type C (HCV). The primary aim of this research proposal is to address a critical gap in liver cancer biology research by employing state-of-the-art cryo-electron tomography (cryo-ET) coupled with advanced computational analysis to investigate the molecular architecture of intact virions at near-atomic resolution and visualize replication intermediates within infected cells and liver cancer biopsies. This will reveal novel mechanistic insights into the key questions of cancer-causing viral biology, particularly the structure, distribution, and conformational states of he...

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Liver cancer is a significant health concern associated with viral hepatitis, particularly hepatitis virus type B (HBV) and type C (HCV). The primary aim of this research proposal is to address a critical gap in liver cancer biology research by employing state-of-the-art cryo-electron tomography (cryo-ET) coupled with advanced computational analysis to investigate the molecular architecture of intact virions at near-atomic resolution and visualize replication intermediates within infected cells and liver cancer biopsies. This will reveal novel mechanistic insights into the key questions of cancer-causing viral biology, particularly the structure, distribution, and conformational states of hepatitis viral surface antigens from native virions, which will inspire new ways to detect and treat viral hepatitis infections. The proposed research will also examine the dynamic process of viral entry and membrane fusion, aiming at providing virus-host cell interactions at the molecular resolution in situ. Additionally, the objective of the research is to uncover the molecular mechanisms underpinning viral replication, particularly the viral replication factories for genome replication and membrane contact sites within remodeled intracellular membranes during the active infection process in both cells and liver cancer tissues, leading to a better understanding of viral infection mechanisms inside intracellular membranous compartments and the development of novel and broad-spectrum therapeutics targeting key processes during viral replication. Collectively, the research aims to make significant contributions to viral hepatitis research, with the ultimate objective of designing more effective approaches to the detection and treatment of viral hepatitis infections, obesity, and liver cancer.

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