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

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...

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Autores principales: Burkard, Thomas, Proske, Nora, Resner, Kathrin, Collignon, Laura, Knegendorf, Leonard, Friesland, Martina, Verhoye, Lieven, Sayed, Ibrahim M., Brüggemann, Yannick, Nocke, Maximilian K., Behrendt, Patrick, Wedemeyer, Heiner, Meuleman, Philip, Todt, Daniel, Steinmann, Eike
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8946046/
https://www.ncbi.nlm.nih.gov/pubmed/35326378
http://dx.doi.org/10.3390/cells11060927
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author Burkard, Thomas
Proske, Nora
Resner, Kathrin
Collignon, Laura
Knegendorf, Leonard
Friesland, Martina
Verhoye, Lieven
Sayed, Ibrahim M.
Brüggemann, Yannick
Nocke, Maximilian K.
Behrendt, Patrick
Wedemeyer, Heiner
Meuleman, Philip
Todt, Daniel
Steinmann, Eike
author_facet Burkard, Thomas
Proske, Nora
Resner, Kathrin
Collignon, Laura
Knegendorf, Leonard
Friesland, Martina
Verhoye, Lieven
Sayed, Ibrahim M.
Brüggemann, Yannick
Nocke, Maximilian K.
Behrendt, Patrick
Wedemeyer, Heiner
Meuleman, Philip
Todt, Daniel
Steinmann, Eike
author_sort Burkard, Thomas
collection PubMed
description 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.
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spelling pubmed-89460462022-03-25 Viral Interference of Hepatitis C and E Virus Replication in Novel Experimental Co-Infection Systems Burkard, Thomas Proske, Nora Resner, Kathrin Collignon, Laura Knegendorf, Leonard Friesland, Martina Verhoye, Lieven Sayed, Ibrahim M. Brüggemann, Yannick Nocke, Maximilian K. Behrendt, Patrick Wedemeyer, Heiner Meuleman, Philip Todt, Daniel Steinmann, Eike Cells Article 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. MDPI 2022-03-08 /pmc/articles/PMC8946046/ /pubmed/35326378 http://dx.doi.org/10.3390/cells11060927 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Burkard, Thomas
Proske, Nora
Resner, Kathrin
Collignon, Laura
Knegendorf, Leonard
Friesland, Martina
Verhoye, Lieven
Sayed, Ibrahim M.
Brüggemann, Yannick
Nocke, Maximilian K.
Behrendt, Patrick
Wedemeyer, Heiner
Meuleman, Philip
Todt, Daniel
Steinmann, Eike
Viral Interference of Hepatitis C and E Virus Replication in Novel Experimental Co-Infection Systems
title Viral Interference of Hepatitis C and E Virus Replication in Novel Experimental Co-Infection Systems
title_full Viral Interference of Hepatitis C and E Virus Replication in Novel Experimental Co-Infection Systems
title_fullStr Viral Interference of Hepatitis C and E Virus Replication in Novel Experimental Co-Infection Systems
title_full_unstemmed Viral Interference of Hepatitis C and E Virus Replication in Novel Experimental Co-Infection Systems
title_short Viral Interference of Hepatitis C and E Virus Replication in Novel Experimental Co-Infection Systems
title_sort viral interference of hepatitis c and e virus replication in novel experimental co-infection systems
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8946046/
https://www.ncbi.nlm.nih.gov/pubmed/35326378
http://dx.doi.org/10.3390/cells11060927
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