Next Article in Journal
Reduced Colonic Mucosal Injury in 2,3,7,8-Tetrachlorodibenzo-p-Dioxin Poly ADP-Ribose Polymerase (TIPARP/PARP7)-Deficient Mice
Previous Article in Journal
Peripheral Nerve Injury Treatments and Advances: One Health Perspective
Previous Article in Special Issue
Knockdown of Mitogen-Activated Protein Kinase Kinase 3 Negatively Regulates Hepatitis A Virus Replication
Article

Domain 2 of Hepatitis C Virus Protein NS5A Activates Glucokinase and Induces Lipogenesis in Hepatocytes

1
CIRI, Centre International de Recherche en Infectiologie, VIRal Infection Metabolism Immunity Team, University of Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, 21 Avenue Tony Garnier, F-69007 Lyon, France
2
CNRS ERL9002-BSI-Integrative Structural Biology, 1 rue du Professeur Calmette, F-59019 Lille, France
3
Université de Lille, INSERM, CHU Lille, Institut Pasteur de Lille, U1167-RID-AGE-Risk Factors and Molecular Determinants of Aging-Related Diseases, 1 rue du Professeur Calmette, F-59019 Lille, France
*
Author to whom correspondence should be addressed.
Current address: IGFL, ENS-Lyon, 32/34 Avenue Tony Garnier, 69007 Lyon, France.
These authors contributed equally to this work.
Academic Editors: Tatsuo Kanda and Shingo Nakamoto
Int. J. Mol. Sci. 2022, 23(2), 919; https://doi.org/10.3390/ijms23020919
Received: 10 December 2021 / Revised: 5 January 2022 / Accepted: 12 January 2022 / Published: 14 January 2022
(This article belongs to the Special Issue Hepatitis Virus Infection and Molecular Research 2021)
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. View Full-Text
Keywords: hepatitis C virus; NS5A; glycolysis; glucokinase; lipogenesis; human lipoprotein; central carbon metabolism; hepatocyte hepatitis C virus; NS5A; glycolysis; glucokinase; lipogenesis; human lipoprotein; central carbon metabolism; hepatocyte
Show Figures

Figure 1

MDPI and ACS Style

Perrin-Cocon, L.; Kundlacz, C.; Jacquemin, C.; Hanoulle, X.; Aublin-Gex, A.; Figl, M.; Manteca, J.; André, P.; Vidalain, P.-O.; Lotteau, V.; Diaz, O. Domain 2 of Hepatitis C Virus Protein NS5A Activates Glucokinase and Induces Lipogenesis in Hepatocytes. Int. J. Mol. Sci. 2022, 23, 919. https://doi.org/10.3390/ijms23020919

AMA Style

Perrin-Cocon L, Kundlacz C, Jacquemin C, Hanoulle X, Aublin-Gex A, Figl M, Manteca J, André P, Vidalain P-O, Lotteau V, Diaz O. Domain 2 of Hepatitis C Virus Protein NS5A Activates Glucokinase and Induces Lipogenesis in Hepatocytes. International Journal of Molecular Sciences. 2022; 23(2):919. https://doi.org/10.3390/ijms23020919

Chicago/Turabian Style

Perrin-Cocon, Laure, Cindy Kundlacz, Clémence Jacquemin, Xavier Hanoulle, Anne Aublin-Gex, Marianne Figl, Jeremy Manteca, Patrice André, Pierre-Olivier Vidalain, Vincent Lotteau, and Olivier Diaz. 2022. "Domain 2 of Hepatitis C Virus Protein NS5A Activates Glucokinase and Induces Lipogenesis in Hepatocytes" International Journal of Molecular Sciences 23, no. 2: 919. https://doi.org/10.3390/ijms23020919

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop