Viral Interference of Hepatitis C and E Virus Replication in Novel Experimental Co-Infection Systems

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), Institute for Experimental Virology, 30625 Hannover, Germany

Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, 30625 Hannover, Germany

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Laboratory of Liver Infectious Diseases, Ghent University, 9000 Gent, Belgium

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Microbiology and Immunology Department, Faculty of Medicine, Assiut University, Assiut 71515, Egypt

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German Centre for Infection Research (DZIF), Partner Site Hannover Braunschweig, 30625 Hannover, Germany

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European Virus Bioinformatics Center (EVBC), 07743 Jena, Germany

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German Centre for Infection Research (DZIF), External Partner Site, 44801 Bochum, Germany

Authors to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

^‡

These authors contributed equally to this work.

Academic Editors: Ana Sofia Coroadinha and Richard J.P. Brown

Cells 2022, 11(6), 927; https://doi.org/10.3390/cells11060927

Received: 14 January 2022 / Revised: 4 March 2022 / Accepted: 4 March 2022 / Published: 8 March 2022

(This article belongs to the Special Issue Cells as Viral Hosts)

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Abstract

Background: Hepatitis C virus (HCV) constitutes a global health problem, while hepatitis E virus (HEV) is the major cause of acute viral hepatitis globally. HCV/HEV co-infections have been poorly characterized, as they are hampered by the lack of robust HEV cell culture systems. This study developed experimental models to study HCV/HEV co-infections and investigate viral interference in cells and humanized mice. Methods: We used state-of-the art human hepatocytes tissue culture models to assess HEV and HCV replication in co- or super-transfection settings. Findings were confirmed by co- and super-infection experiments in human hepatocytes and in vivo in human liver chimeric mice. Results: HEV was inhibited by concurrent HCV replication in human hepatocytes. This exclusion phenotype was linked to the protease activity of HCV. These findings were corroborated by the fact that in HEV on HCV super-infected mice, HEV viral loads were reduced in individual mice. Similarly, HCV on HEV super-infected mice showed reduced HCV viral loads. Conclusion: Direct interference of both viruses with HCV NS3/4A as the determinant was observed. In vivo, we detected reduced replication of both viruses after super-infection in individual mice. These findings provide new insights into the pathogenesis of HCV-HEV co-infections and should contribute to its clinical management in the future. View Full-Text

Keywords: Hepatitis C virus (HCV); Hepatitis E virus (HEV); co-infection; human hepatocytes; sofosbuvir; HCV protease; human liver chimeric mice

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MDPI and ACS Style

Burkard, T.; Proske, N.; Resner, K.; Collignon, L.; Knegendorf, L.; Friesland, M.; Verhoye, L.; Sayed, I.M.; Brüggemann, Y.; Nocke, M.K.; Behrendt, P.; Wedemeyer, H.; Meuleman, P.; Todt, D.; Steinmann, E. Viral Interference of Hepatitis C and E Virus Replication in Novel Experimental Co-Infection Systems. Cells 2022, 11, 927. https://doi.org/10.3390/cells11060927

AMA Style

Burkard T, Proske N, Resner K, Collignon L, Knegendorf L, Friesland M, Verhoye L, Sayed IM, Brüggemann Y, Nocke MK, Behrendt P, Wedemeyer H, Meuleman P, Todt D, Steinmann E. Viral Interference of Hepatitis C and E Virus Replication in Novel Experimental Co-Infection Systems. Cells. 2022; 11(6):927. https://doi.org/10.3390/cells11060927

Chicago/Turabian Style

Burkard, Thomas, Nora Proske, Kathrin Resner, Laura Collignon, Leonard Knegendorf, Martina Friesland, Lieven Verhoye, Ibrahim M. Sayed, Yannick Brüggemann, Maximilian K. Nocke, Patrick Behrendt, Heiner Wedemeyer, Philip Meuleman, Daniel Todt, and Eike Steinmann. 2022. "Viral Interference of Hepatitis C and E Virus Replication in Novel Experimental Co-Infection Systems" Cells 11, no. 6: 927. https://doi.org/10.3390/cells11060927

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Viral Interference of Hepatitis C and E Virus Replication in Novel Experimental Co-Infection Systems

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