Identification of Keratin 23 as a Hepatitis C Virus-Induced Host Factor in the Human Liver
Volker Kinast,
Stefan L. Leber,
Richard J. P. Brown,
Gabrielle Vieyres,
Patrick Behrendt,
Constanze Eßbach,
Pavel Strnad,
Florian W. R. Vondran,
Markus Cornberg,
Cora Wex,
Thomas Pietschmann,
Johannes Haybaeck,
Daniel Todt,
Eike Steinmann
Affiliations
Volker Kinast
Ruhr University Bochum, Faculty of Medicine, Department for Molecular and Medical Virology, 44801 Bochum, Germany
Stefan L. Leber
Department of Pathology, Otto-von-Guericke University of Magdeburg, 39106 Magdeburg, Germany
Richard J. P. Brown
Division of Veterinary Medicine, Paul Ehrlich Institute, 63225 Langen, Germany
Gabrielle Vieyres
Institute of Experimental Virology, Twincore Centre for Experimental and Clinical Infection Research, a joint venture between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI), 30625 Hannover, Germany
Patrick Behrendt
Institute of Experimental Virology, Twincore Centre for Experimental and Clinical Infection Research, a joint venture between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI), 30625 Hannover, Germany
Constanze Eßbach
Department of Pathology, Otto-von-Guericke University of Magdeburg, 39106 Magdeburg, Germany
Pavel Strnad
Department of Internal Medicine III, University Hospital Aachen, 52074 Aachen, Germany
Florian W. R. Vondran
German Center for Infection Research (DZIF), Partner Site Hannover-Braunschweig, 30625 Hannover, Germany
Markus Cornberg
Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, 30625 Hannover, Germany
Cora Wex
Department of General, Visceral, Vascular and Transplantation Surgery, Otto-von-Guericke University of Magdeburg, 39106 Magdeburg, Germany
Thomas Pietschmann
Institute of Experimental Virology, Twincore Centre for Experimental and Clinical Infection Research, a joint venture between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI), 30625 Hannover, Germany
Johannes Haybaeck
Department of Pathology, Otto-von-Guericke University of Magdeburg, 39106 Magdeburg, Germany
Daniel Todt
Ruhr University Bochum, Faculty of Medicine, Department for Molecular and Medical Virology, 44801 Bochum, Germany
Eike Steinmann
Ruhr University Bochum, Faculty of Medicine, Department for Molecular and Medical Virology, 44801 Bochum, Germany
Keratin proteins form intermediate filaments, which provide structural support for many tissues. Multiple keratin family members are reported to be associated with the progression of liver disease of multiple etiologies. For example, keratin 23 (KRT23) was reported as a stress-inducible protein, whose expression levels correlate with the severity of liver disease. Hepatitis C virus (HCV) is a human pathogen that causes chronic liver diseases including fibrosis, cirrhosis, and hepatocellular carcinoma. However, a link between KRT23 and hepatitis C virus (HCV) infection has not been reported previously. In this study, we investigated KRT23 mRNA levels in datasets from liver biopsies of chronic hepatitis C (CHC) patients and in primary human hepatocytes experimentally infected with HCV, in addition to hepatoma cells. Interestingly, in each of these specimens, we observed an HCV-dependent increase of mRNA levels. Importantly, the KRT23 protein levels in patient plasma decreased upon viral clearance. Ectopic expression of KRT23 enhanced HCV infection; however, CRIPSPR/Cas9-mediated knockout did not show altered replication efficiency. Taken together, our study identifies KRT23 as a novel, virus-induced host-factor for hepatitis C virus.
