ArticlePLoS pathogens2021
Aerobic glycolysis supports hepatitis B virus protein synthesis through interaction between viral surface antigen and pyruvate kinase isoform M2.
Article in PLoS pathogens, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 48 citations in OpenAlex.
- Targeting Pyruvate Kinase M2: Signal Transduction Pathways and Exploration of Cancer Therapeutic Strategies.The AAPS journal · 2026Review
- Acetyl-coenzyme A synthetase 2-mediated acetyl-coenzyme A accumulation promotes mitophagy and tumor growth via increased H3K27ac in hepatitis B virus-related hepatocellular carcinoma.Clinical and molecular hepatology · 2026Article
- Blocking Lysine Crotonylation and Aerobic Glycolysis as Targeting Strategy Against mpox Virus Replication.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Regulation of hepatitis B virus cccDNA by metabolic pathways: Editorial on "GDH1-dependent α-ketoglutarate promotes HBV transcription by modulating histone methylations on the cccDNA minichromosome".Clinical and molecular hepatology · 2026Article
- Review
- An overview of hepatitis B virus in gastric carcinogenesis: from clinical association to molecular mechanisms.Infectious agents and cancer · 2025Review
- HBV and host metabolic crosstalk: Reprogramming pathways for viral replication and pathogenesis.Virologica Sinica · 2025Review
- Pyruvate Kinase M2 Links Metabolism and Epigenetics: A New Target for Liver Disease Treatment.Biomolecules · 2025Review
- Article
- Metabolism-associated protein network constructing and host-directed anti-influenza drug repurposing.Briefings in bioinformatics · 2025Article
- Hepatitis B surface antigen: carcinogenesis mechanisms and clinical implications in hepatocellular carcinoma.Experimental hematology & oncology · 2025Review
- Glucose-independent human cytomegalovirus replication is supported by metabolites that feed upper glycolytic branches.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Matrix Protein of Vesicular Stomatitis Virus Targets the Mitochondria, Reprograms Glucose Metabolism, and Sensitizes to 2-Deoxyglucose in Glioblastoma.Human gene therapy · 2024Article
- Understanding lactate in the development of Hepatitis B virus-related hepatocellular carcinoma.Infectious agents and cancer · 2024Review
- The novel mechanism facilitating chronic hepatitis B infection: immunometabolism and epigenetic modification reprogramming.Frontiers in immunology · 2024Review
- Redox Regulation and Metabolic Dependency of Zika Virus Replication: Inhibition by Nrf2-Antioxidant Response and NAD(H) Antimetabolites.Journal of virology · 2023Article
- Picornavirus infection enhances aspartate by the SLC38A8 transporter to promote viral replication.PLoS pathogens · 2023Article
- Review
- A viral interferon regulatory factor degrades RNA-binding protein hnRNP Q1 to enhance aerobic glycolysis via recruiting E3 ubiquitin ligase KLHL3 and decaying GDPD1 mRNA.Cell death and differentiation · 2022Article
- Effect of Lactate on Epigenetic Regulation in the Development of Hepatitis B Virus-related Hepatocellular Carcinoma.Journal of clinical and translational hepatology · 2022Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
As an intracellular pathogen, the reproduction of the hepatitis B virus (HBV) depends on the occupancy of host metabolism machinery. Here we test a hypothesis if HBV may govern intracellular biosynthesis to achieve a productive reproduction. To test this hypothesis, we set up an affinity purification screen for host factors that interact with large viral surface antigens (LHBS). This identified pyruvate kinase isoform M2 (PKM2), a key regulator of glucose metabolism, as a binding partner of viral surface antigens. We showed that the expression of viral LHBS affected oligomerization of PKM2 in hepatocytes, thereby increasing glucose consumption and lactate production, a phenomenon known as aerobic glycolysis. Reduction of PKM2 activity was also validated in several different models, including HBV-infected HepG2-NTCP-C4 cells, adenovirus mediated HBV gene transduction and transfection with a plasmid containing complete HBV genome on HuH-7 cells. We found the recovery of PKM2 activity in hepatocytes by chemical activators, TEPP-46 or DASA-58, reduced expressions of viral surface and core antigens. In addition, reduction of glycolysis by culturing in low-glucose condition or treatment with 2-deoxyglucose also decreased expressions of viral surface antigen, without affecting general host proteins. Finally, TEPP-46 largely suppressed proliferation of LHBS-positive cells on 3-dimensional agarose plates, but showed no effect on the traditional 2-dimensional cell culture. Taken together, these results indicate that HBV-induced metabolic switch may support its own translation in hepatocytes. In addition, aerobic glycolysis is likely essential for LHBS-mediated oncogenesis. Accordingly, restriction of glucose metabolism may be considered as a novel strategy to restrain viral protein synthesis and subsequent oncogenesis during chronic HBV infection.
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