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  1. Article ; Online: Domain 2 of Hepatitis C Virus Protein NS5A Activates Glucokinase and Induces Lipogenesis in Hepatocytes

    Laure Perrin-Cocon / Cindy Kundlacz / Clémence Jacquemin / Xavier Hanoulle / Anne Aublin-Gex / Marianne Figl / Jeremy Manteca / Patrice André / Pierre-Olivier Vidalain / Vincent Lotteau / Olivier Diaz

    International Journal of Molecular Sciences, Vol 23, Iss 919, p

    2022  Volume 919

    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 ... ...

    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.
    Keywords hepatitis C virus ; NS5A ; glycolysis ; glucokinase ; lipogenesis ; human lipoprotein ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 570
    Language English
    Publishing date 2022-01-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: A hexokinase isoenzyme switch in human liver cancer cells promotes lipogenesis and enhances innate immunity

    Laure Perrin-Cocon / Pierre-Olivier Vidalain / Clémence Jacquemin / Anne Aublin-Gex / Keedrian Olmstead / Baptiste Panthu / Gilles Jeans Philippe Rautureau / Patrice André / Piotr Nyczka / Marc-Thorsten Hütt / Nivea Amoedo / Rodrigue Rossignol / Fabian Volker Filipp / Vincent Lotteau / Olivier Diaz

    Communications Biology, Vol 4, Iss 1, Pp 1-

    2021  Volume 15

    Abstract: Many cancers fuel their rapid growth by replacing glucokinase with its higher affinity isoenzyme, hexokinase 2 (HK2), making HK2 an attractive drug target. In this study, Perrin-Cocon and Vidalain et al. use CRISPR/Cas-9 gene editing to reverse this ... ...

    Abstract Many cancers fuel their rapid growth by replacing glucokinase with its higher affinity isoenzyme, hexokinase 2 (HK2), making HK2 an attractive drug target. In this study, Perrin-Cocon and Vidalain et al. use CRISPR/Cas-9 gene editing to reverse this enzymatic switch in human liver cancer cells, and find this restores innate immune function as well as reversing cancer-associated metabolic reprogramming.
    Keywords Biology (General) ; QH301-705.5
    Language English
    Publishing date 2021-02-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: The interactomes of influenza virus NS1 and NS2 proteins identify new host factors and provide insights for ADAR1 playing a supportive role in virus replication.

    Benoît de Chassey / Anne Aublin-Gex / Alessia Ruggieri / Laurène Meyniel-Schicklin / Fabrine Pradezynski / Nathalie Davoust / Thibault Chantier / Lionel Tafforeau / Philippe-Emmanuel Mangeot / Claire Ciancia / Laure Perrin-Cocon / Ralf Bartenschlager / Patrice André / Vincent Lotteau

    PLoS Pathogens, Vol 9, Iss 7, p e

    2013  Volume 1003440

    Abstract: Influenza A NS1 and NS2 proteins are encoded by the RNA segment 8 of the viral genome. NS1 is a multifunctional protein and a virulence factor while NS2 is involved in nuclear export of viral ribonucleoprotein complexes. A yeast two-hybrid screening ... ...

    Abstract Influenza A NS1 and NS2 proteins are encoded by the RNA segment 8 of the viral genome. NS1 is a multifunctional protein and a virulence factor while NS2 is involved in nuclear export of viral ribonucleoprotein complexes. A yeast two-hybrid screening strategy was used to identify host factors supporting NS1 and NS2 functions. More than 560 interactions between 79 cellular proteins and NS1 and NS2 proteins from 9 different influenza virus strains have been identified. These interacting proteins are potentially involved in each step of the infectious process and their contribution to viral replication was tested by RNA interference. Validation of the relevance of these host cell proteins for the viral replication cycle revealed that 7 of the 79 NS1 and/or NS2-interacting proteins positively or negatively controlled virus replication. One of the main factors targeted by NS1 of all virus strains was double-stranded RNA binding domain protein family. In particular, adenosine deaminase acting on RNA 1 (ADAR1) appeared as a pro-viral host factor whose expression is necessary for optimal viral protein synthesis and replication. Surprisingly, ADAR1 also appeared as a pro-viral host factor for dengue virus replication and directly interacted with the viral NS3 protein. ADAR1 editing activity was enhanced by both viruses through dengue virus NS3 and influenza virus NS1 proteins, suggesting a similar virus-host co-evolution.
    Keywords Immunologic diseases. Allergy ; RC581-607 ; Biology (General) ; QH301-705.5
    Subject code 570
    Language English
    Publishing date 2013-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

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    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

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