Cellular stress response during hepatitis C virus infection: a balancing act between viral persistence and host cell survival

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    Abstract

    Hepatitis C virus (HCV) is a virus that infects hepatocytes, the parenchymal liver cells. HCV infection causes acute and chronic liver disease and is associated with cirrhosis and development of liver cancer. Approximately 80 million people worldwide are infected with HCV and 400,000 individuals die each year due the infection. In recent years our understanding of HCV has improved significantly and it is expected that in 2030 HCV infections will be eliminated. Despite advances in antiviral drug treatment and knowledge on HCV, there are still important challenges to be addressed such as the development of an effective vaccine and unraveling virus-host interactions.
    During natural HCV infection, hepatocytes have to deal with: 1) HCV replication and expression of viral proteins and 2) with the host antiviral immune response. To deal simultaneously with multiple stresses, the hepatocytes require adaptive responses. The major stresses resulting from viral infection and replication are oxidative stress and endoplasmic reticulum (ER) stress. Indeed, some of the viral proteins, in particular the proteins Core, NS3/4A and NS5A are strong pro-oxidants.
    In this thesis, we focus on the adaptation of hepatocytes to cellular stress induced by HCV virus proteins Core, NS3/4A and NS5A. Furthermore, we have also investigated the interaction between infected and stressed hepatocytes on hepatic stellate cells, the principal cell type involved in liver fibrosis. Finally, we speculate whether the adaptive response to cellular stress in hepatocytes plays a major role in the control of HCV infection and therefore could be a target for therapeutic intervention.
    Original languageEnglish
    QualificationDoctor of Philosophy
    Awarding Institution
    • University of Groningen
    Supervisors/Advisors
    • Moshage, Han, Supervisor
    • Daemen, Toos, Supervisor
    • Faber, Klaas Nico, Supervisor
    • Navas, M.C., Supervisor, External person
    • Reggiori, Fulvio, Assessment committee
    • Olinga, Peter, Assessment committee
    • Odenthal, M., Assessment committee, External person
    Award date10-Oct-2018
    Place of Publication[Groningen]
    Publisher
    Print ISBNs978-94-034-1048-7
    Electronic ISBNs978-94-034-1047-0
    Publication statusPublished - 2018

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