ArticleInternational journal of molecular sciences2022
Domain 2 of Hepatitis C Virus Protein NS5A Activates Glucokinase and Induces Lipogenesis in Hepatocytes.
Article in International journal of molecular sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 16 citations in OpenAlex.
- HBV/HCV coinfection and anti-tuberculosis drug-induced liver injury: from risk assessment and exploration of mechanisms to preventive considerations.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2026Review
- Hepatocyte Models for Metabolic Dysfunction-Associated Steatotic Liver Disease: A Comparative Analysis of Non-HepG2 Cell Models.International journal of molecular sciences · 2026Review
- Nicotinamide metabolism is essential for Hepatitis C Virus replication and the production of infectious Lipo-Viro-Particles.PLoS pathogens · 2026Article
- Article
- Network pharmacology and molecular docking reveal antiviral mechanisms of silver nanoparticles synthesized by Oscillatoria sp. against HCV pathogenesis.Scientific reports · 2025Article
- Article
- Foot-and-mouth disease virus activates glycolysis and hijacks HK2 to inhibit innate immunity and promote viral replication.Veterinary research · 2025Article
- Deformed wing virus coopts the host arginine kinase to enhance its fitness in honey bees (Apis mellifera).BMC biology · 2025Article
- After the Storm: Persistent Molecular Alterations Following HCV Cure.International journal of molecular sciences · 2024Review
- Talk to Me-Interplay between Mitochondria and Microbiota in Aging.International journal of molecular sciences · 2023Review
- Article
- Review
- Hepatitis A Virus Infection and Molecular Research.International journal of molecular sciences · 2022Article
- What role for cellular metabolism in the control of hepatitis viruses?Frontiers in immunology · 2022Review
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Hepatitis C virus (HCV) relies on cellular lipid metabolism for its replication, and actively modulates lipogenesis and lipid trafficking in infected hepatocytes. This translates into an intracellular accumulation of triglycerides leading to liver steatosis, cirrhosis and hepatocellular carcinoma, which are hallmarks of HCV pathogenesis. While the interaction of HCV with hepatocyte metabolic pathways is patent, how viral proteins are able to redirect central carbon metabolism towards lipogenesis is unclear. Here, we report that the HCV protein NS5A activates the glucokinase (GCK) isoenzyme of hexokinases through its D2 domain (NS5A-D2). GCK is the first rate-limiting enzyme of glycolysis in normal hepatocytes whose expression is replaced by the hexokinase 2 (HK2) isoenzyme in hepatocellular carcinoma cell lines. We took advantage of a unique cellular model specifically engineered to re-express GCK instead of HK2 in the Huh7 cell line to evaluate the consequences of NS5A-D2 expression on central carbon and lipid metabolism. NS5A-D2 increased glucose consumption but decreased glycogen storage. This was accompanied by an altered mitochondrial respiration, an accumulation of intracellular triglycerides and an increased production of very-low density lipoproteins. Altogether, our results show that NS5A-D2 can reprogram central carbon metabolism towards a more energetic and glycolytic phenotype compatible with HCV needs for replication.
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