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 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.
Author: | Thomas BurkardORCiDGND, Nora ProskeGND, Kathrin ResnerGND, Laura CollignonORCiDGND, Leonard KnegendorfORCiDGND, Martina FrieslandGND, Lieven VerhoyeGND, Ibrahim M. SayedORCiDGND, Yannick BrüggemannGND, Maximilian K. NockeORCiDGND, Patrick BehrendtGND, Heiner WedemeyerGND, Philip MeulemanGND, Daniel Matthias TodtORCiDGND, Eike SteinmannORCiDGND |
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URN: | urn:nbn:de:hbz:294-90638 |
DOI: | https://doi.org/10.3390/cells11060927 |
Parent Title (English): | Cells |
Publisher: | MDPI |
Place of publication: | Basel |
Document Type: | Article |
Language: | English |
Date of Publication (online): | 2022/06/24 |
Date of first Publication: | 2022/03/08 |
Publishing Institution: | Ruhr-Universität Bochum, Universitätsbibliothek |
Tag: | Open Access Fonds HCV protease; Hepatitis C virus (HCV); Hepatitis E virus (HEV); co-infection; human hepatocytes; human liver chimeric mice; sofosbuvir |
Volume: | 11 |
Issue: | 6, Article 927 |
First Page: | 927-1 |
Last Page: | 927-18 |
Note: | Article Processing Charge funded by the Deutsche Forschungsgemeinschaft (DFG) and the Open Access Publication Fund of Ruhr-Universität Bochum. |
Institutes/Facilities: | Institut für Hygiene und Mikrobiologie, Abteilung für Molekulare und Medizinische Virologie |
Institut für Hygiene und Mikrobiologie | |
Medizinische Fakultät, Abteilung für Molekulare und Medizinische Virologie | |
Dewey Decimal Classification: | Technik, Medizin, angewandte Wissenschaften / Medizin, Gesundheit |
open_access (DINI-Set): | open_access |
faculties: | Medizinische Fakultät |
Licence (English): | Creative Commons - CC BY 4.0 - Attribution 4.0 International |