Characterisation of liver pathogenesis, human immune responses and drug testing in a humanised mouse model of HCV infection

Gut. 2016 Oct;65(10):1744-53. doi: 10.1136/gutjnl-2014-307856. Epub 2015 Jul 6.


Objective: HCV infection affects millions of people worldwide, and many patients develop chronic infection leading to liver cancers. For decades, the lack of a small animal model that can recapitulate HCV infection, its immunopathogenesis and disease progression has impeded the development of an effective vaccine and therapeutics. We aim to provide a humanised mouse model for the understanding of HCV-specific human immune responses and HCV-associated disease pathologies.

Design: Recently, we have established human liver cells with a matched human immune system in NOD-scid Il2rg(-/-) (NSG) mice (HIL mice). These mice are infected with HCV by intravenous injection, and the pathologies are investigated.

Results: In this study, we demonstrate that HIL mouse is capable of supporting HCV infection and can present some of the clinical symptoms found in HCV-infected patients including hepatitis, robust virus-specific human immune cell and cytokine responses as well as liver fibrosis and cirrhosis. Similar to results obtained from the analysis of patient samples, the human immune cells, particularly T cells and macrophages, play critical roles during the HCV-associated liver disease development in the HIL mice. Furthermore, our model is demonstrated to be able to reproduce the therapeutic effects of human interferon alpha 2a antiviral treatment.

Conclusions: The HIL mouse provides a model for the understanding of HCV-specific human immune responses and HCV-associated disease pathologies. It could also serve as a platform for antifibrosis and immune-modulatory drug testing.


MeSH terms

  • Animals
  • Antiviral Agents / therapeutic use
  • Disease Models, Animal*
  • Hepatitis C, Chronic* / drug therapy
  • Hepatitis C, Chronic* / immunology
  • Hepatitis C, Chronic* / physiopathology
  • Humans
  • Immunity, Cellular / immunology
  • Interferon alpha-2
  • Interferon-alpha / therapeutic use*
  • Mice
  • Mice, Inbred NOD*
  • Recombinant Proteins / therapeutic use
  • Reproducibility of Results


  • Antiviral Agents
  • Interferon alpha-2
  • Interferon-alpha
  • Recombinant Proteins