Aerobic glycolysis supports hepatitis B virus protein synthesis through interaction between viral surface antigen and pyruvate kinase isoform M2

As an intracellular pathogen, the reproduction of hepatitis B virus (HBV) depends on occupancy host metabolism machinery. Here we test a hypothesis if HBV may govern biosynthesis to achieve productive reproduction. To this hypothesis, set up affinity purification screen for factors that interact with large viral surface antigens (LHBS). This identified pyruvate kinase isoform M2 (PKM2), key regulator glucose metabolism, as binding partner antigens. We showed expression LHBS affected oligomerization PKM2 in hepatocytes, thereby increasing consumption and lactate production, phenomenon known aerobic glycolysis. Reduction activity was also validated several different models, including HBV-infected HepG2-NTCP-C4 cells, adenovirus mediated gene transduction transfection plasmid containing complete genome HuH-7 cells. found recovery hepatocytes by chemical activators, TEPP-46 or DASA-58, reduced expressions core In addition, reduction glycolysis culturing low-glucose condition treatment 2-deoxyglucose decreased antigen, without affecting general proteins. Finally, largely suppressed proliferation LHBS-positive cells 3-dimensional agarose plates, but no effect traditional 2-dimensional cell culture. Taken together, these results indicate HBV-induced metabolic switch support its own translation hepatocytes. is likely essential LHBS-mediated oncogenesis. Accordingly, restriction be considered novel strategy restrain protein synthesis subsequent oncogenesis during chronic infection.