2026-04-06 ロックフェラー大学
＜関連情報＞
- https://www.rockefeller.edu/news/39337-a-new-mouse-model-of-virus-driven-liver-cancer-may-open-the-door-to-better-diagnosis-and-treatments/
- https://www.sciencedirect.com/science/article/pii/S0168827826000851?via%3Dihub
ウイルス誘発性肝線維症および肝細胞癌の免疫能を有するマウスモデル An immunocompetent murine model of virus-elicited liver fibrosis and hepatocellular carcinoma
Mariana Nogueira Batista, Juliano Bordignon, Ana Luiza Pamplona Mosimann, Tesia Bobrowski, Hsuan-An Chen, Gabriel Tobin-Xet, Erika Ashihara Barrall, Nataliya Prokhnevska, Abishek Balachandra Vaidya, Tyler Lewy, Kenneth Harold Dinnon III, Leon Louis Seifert, Briana Zeck, Corrine Quirk, Yu-Jui Ho, Aveline Filliol, Raphael Wolfisberg, Caroline Jiang, Bruno Cogliati, Luis Chiriboga …Charles Moen Rice
Journal of Hepatology Available online: 11 March 2026
DOI:https://doi.org/10.1016/j.jhep.2026.02.020
Graphical abstract
Highlights
- First immunocompetent mouse model in which chronic hepacivirus infection induces progressive liver damage and HCC
- Chronic NrHV infection shares many histological and molecular features with chronic hepatitis C virus infection
- NrHV-associated tumors are well-differentiated, steatotic and inflamed
- NrHV-associated HCC is highly heterogeneous with regard to gene expression and putative oncogenic driver mutations
Abstract
Background & Aims
Hepatocellular carcinoma (HCC) is the third deadliest cancer worldwide. Over 75% of HCC cases are associated with chronic viral infections. Mechanistic studies and preclinical therapeutic development for virus-associated HCC have been limited by a paucity of small animal models of chronic hepatotropic virus infection that faithfully recapitulate human disease.
Methods and Results
Here we demonstrate the induction of chronic hepatitis, progressive liver fibrosis, and HCC in immunocompetent laboratory mice upon chronic viral infection with Norway rat hepacivirus (NrHV) – a virus closely related to hepatitis C virus (HCV). NrHV-elicited tumors resemble HCV-associated tumors and liver transcriptome analyses reveal numerous similarities between chronic NrHV and HCV.
Conclusions
These findings establish an experimentally tractable, physiologically relevant, and immunocompetent mouse model of virus-elicited progressive liver fibrosis and oncogenesis.
Impact and implications
(lay summary); The NrHV-HCC model represents the first immunocompetent infectious system that faithfully recapitulates the multistage progression from chronic viral hepatitis to spontaneous hepatocellular carcinoma, bridging a long-standing translational gap between mechanistic mouse studies and human liver cancer. By mirroring the immunopathological, molecular, and sex-associated features of chronic HCV infection, this model provides an unparalleled platform to investigate virus-host interactions underlying fibrosis and oncogenesis. High HCC penetrance and the genetically tractable C57BL/6 background further enhance experimental utility, enabling precise mechanistic dissection and genetic manipulation in a physiologically relevant setting. The capacity to study spontaneous tumor development in the context of natural infection allows for rigorous testing of antifibrotic and anti-cancer strategies, while the persistence of oncogenic potential after viral clearance raises important questions about irreversible disease reprogramming and elevated cancer risk following viral cure – issues of direct relevance to patients cured of HCV.
