Theoretical modeling of hepatitis C acute infection in liver-humanized mice support pre-clinical assessment of candidate viruses for controlled-human-infection studies
Abstract Designing and carrying out a controlled human infection (CHI) model for hepatitis C virus (HCV) is critical for vaccine development. However, key considerations for a CHI model protocol include understanding of the earliest viral-host kinetic events during the acute phase and susceptibility...
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Nature Portfolio
2024-12-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-024-83104-0 |
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| author | Zhenzhen Shi Adquate Mhlanga Yuji Ishida Ari Josephson Nicholson T. Collier Hiromi Abe-Chayama Chise Tateno-Mukaidani Scott J. Cotler Jonathan Ozik Marian Major Jordan J. Feld Kazuaki Chayama Harel Dahari |
| author_facet | Zhenzhen Shi Adquate Mhlanga Yuji Ishida Ari Josephson Nicholson T. Collier Hiromi Abe-Chayama Chise Tateno-Mukaidani Scott J. Cotler Jonathan Ozik Marian Major Jordan J. Feld Kazuaki Chayama Harel Dahari |
| author_sort | Zhenzhen Shi |
| collection | DOAJ |
| description | Abstract Designing and carrying out a controlled human infection (CHI) model for hepatitis C virus (HCV) is critical for vaccine development. However, key considerations for a CHI model protocol include understanding of the earliest viral-host kinetic events during the acute phase and susceptibility of the viral isolate under consideration for use in the CHI model to antiviral treatment before any infections in human volunteers can take place. Humanized mouse models lack adaptive immune responses but provide a unique opportunity to obtain quantitative understanding of early HCV kinetics and develop mathematical models to further understand viral and innate immune response dynamics during acute HCV infection. We show that the models reproduce the measured HCV kinetics in humanized mice, which are consistent with early acute HCV-host dynamics in immunocompetent chimpanzees. Our findings suggest that humanized mice are well-suited to support development of a CHI model. In-silico and in-vivo modeling estimates provide a starting point to characterize candidate viruses for testing in CHI model studies. |
| format | Article |
| id | doaj-art-4e3cd225b79340f986f392ce308ccdaf |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-4e3cd225b79340f986f392ce308ccdaf2025-01-05T12:29:31ZengNature PortfolioScientific Reports2045-23222024-12-0114111210.1038/s41598-024-83104-0Theoretical modeling of hepatitis C acute infection in liver-humanized mice support pre-clinical assessment of candidate viruses for controlled-human-infection studiesZhenzhen Shi0Adquate Mhlanga1Yuji Ishida2Ari Josephson3Nicholson T. Collier4Hiromi Abe-Chayama5Chise Tateno-Mukaidani6Scott J. Cotler7Jonathan Ozik8Marian Major9Jordan J. Feld10Kazuaki Chayama11Harel Dahari12The Program for Experimental and Theoretical Modeling, Division of Hepatology, Department of Medicine, Stritch School of Medicine, Loyola University ChicagoThe Program for Experimental and Theoretical Modeling, Division of Hepatology, Department of Medicine, Stritch School of Medicine, Loyola University ChicagoPhoenixBio Co., Ltd.The Program for Experimental and Theoretical Modeling, Division of Hepatology, Department of Medicine, Stritch School of Medicine, Loyola University ChicagoDecision and Infrastructure Sciences Division, Argonne National LaboratoryCenter for Medical Specialist Graduate Education and Research, Hiroshima UniversityPhoenixBio Co., Ltd.The Program for Experimental and Theoretical Modeling, Division of Hepatology, Department of Medicine, Stritch School of Medicine, Loyola University ChicagoDecision and Infrastructure Sciences Division, Argonne National LaboratoryDivision of Viral Products, Center for Biologics Evaluation and Research, Food and Drug AdministrationToronto Centre for Liver Disease, Toronto General Hospital, University Health NetworkHiroshima Institute of Life SciencesThe Program for Experimental and Theoretical Modeling, Division of Hepatology, Department of Medicine, Stritch School of Medicine, Loyola University ChicagoAbstract Designing and carrying out a controlled human infection (CHI) model for hepatitis C virus (HCV) is critical for vaccine development. However, key considerations for a CHI model protocol include understanding of the earliest viral-host kinetic events during the acute phase and susceptibility of the viral isolate under consideration for use in the CHI model to antiviral treatment before any infections in human volunteers can take place. Humanized mouse models lack adaptive immune responses but provide a unique opportunity to obtain quantitative understanding of early HCV kinetics and develop mathematical models to further understand viral and innate immune response dynamics during acute HCV infection. We show that the models reproduce the measured HCV kinetics in humanized mice, which are consistent with early acute HCV-host dynamics in immunocompetent chimpanzees. Our findings suggest that humanized mice are well-suited to support development of a CHI model. In-silico and in-vivo modeling estimates provide a starting point to characterize candidate viruses for testing in CHI model studies.https://doi.org/10.1038/s41598-024-83104-0Hepatitis C virusAgent-based modelingOrdinary differential equationsLiver-humanized mouse modelControlled human infection model |
| spellingShingle | Zhenzhen Shi Adquate Mhlanga Yuji Ishida Ari Josephson Nicholson T. Collier Hiromi Abe-Chayama Chise Tateno-Mukaidani Scott J. Cotler Jonathan Ozik Marian Major Jordan J. Feld Kazuaki Chayama Harel Dahari Theoretical modeling of hepatitis C acute infection in liver-humanized mice support pre-clinical assessment of candidate viruses for controlled-human-infection studies Scientific Reports Hepatitis C virus Agent-based modeling Ordinary differential equations Liver-humanized mouse model Controlled human infection model |
| title | Theoretical modeling of hepatitis C acute infection in liver-humanized mice support pre-clinical assessment of candidate viruses for controlled-human-infection studies |
| title_full | Theoretical modeling of hepatitis C acute infection in liver-humanized mice support pre-clinical assessment of candidate viruses for controlled-human-infection studies |
| title_fullStr | Theoretical modeling of hepatitis C acute infection in liver-humanized mice support pre-clinical assessment of candidate viruses for controlled-human-infection studies |
| title_full_unstemmed | Theoretical modeling of hepatitis C acute infection in liver-humanized mice support pre-clinical assessment of candidate viruses for controlled-human-infection studies |
| title_short | Theoretical modeling of hepatitis C acute infection in liver-humanized mice support pre-clinical assessment of candidate viruses for controlled-human-infection studies |
| title_sort | theoretical modeling of hepatitis c acute infection in liver humanized mice support pre clinical assessment of candidate viruses for controlled human infection studies |
| topic | Hepatitis C virus Agent-based modeling Ordinary differential equations Liver-humanized mouse model Controlled human infection model |
| url | https://doi.org/10.1038/s41598-024-83104-0 |
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