Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pone.0184127
Title: Hepatitis C virus mediated chronic inflammation and tumorigenesis in the humanised immune system and liver mouse model
Authors: Zheng Z. 
Sze C.W. 
Keng C.T.
Al-Haddawi M.
Liu M.
Tan S.Y.
Kwek H.L.
Her Z.
Chan X.Y.
Barnwal B.
Loh E.
Chang K.T.E. 
Tan T.C. 
Tan Y.-J. 
Chen Q. 
Keywords: gamma interferon
interleukin 10
interleukin 12p70
interleukin 17
interleukin 18
interleukin 23
interleukin 6
interleukin 8
monocyte chemotactic protein 1
virus RNA
biological marker
CD68 antigen, human
cytokine
differentiation antigen
leukocyte antigen
serum albumin
animal experiment
animal model
Article
clinical feature
controlled study
disease association
disease model
granulomatosis
hepatitis C
Hepatitis C virus
human
human tissue
immune response
immune system
immunocompetent cell
incidence
liver adenoma
liver carcinogenesis
liver cell carcinoma
liver fibrosis
macrophage
monocyte
mouse
nonhuman
pathogenesis
phenotype
RNA analysis
T lymphocyte
viremia
animal
blood
Carcinoma, Hepatocellular
cell transformation
chronic hepatitis C
complication
Hepacivirus
immunology
liver function test
Liver Neoplasms
metabolism
pathology
T lymphocyte subpopulation
virology
Animals
Antigens, CD
Antigens, Differentiation, Myelomonocytic
Biomarkers
Carcinoma, Hepatocellular
Cell Transformation, Neoplastic
Cytokines
Disease Models, Animal
Hepacivirus
Hepatitis C, Chronic
Liver Function Tests
Liver Neoplasms
Macrophages
Mice
Monocytes
Serum Albumin
T-Lymphocyte Subsets
Viremia
Issue Date: 2017
Publisher: Public Library of Science
Citation: Zheng Z., Sze C.W., Keng C.T., Al-Haddawi M., Liu M., Tan S.Y., Kwek H.L., Her Z., Chan X.Y., Barnwal B., Loh E., Chang K.T.E., Tan T.C., Tan Y.-J., Chen Q. (2017). Hepatitis C virus mediated chronic inflammation and tumorigenesis in the humanised immune system and liver mouse model. PLoS ONE 12 (9) : e0184127. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0184127
Abstract: Hepatitis C is a liver disease caused by infection of the Hepatitis C virus (HCV). Many individuals infected by the virus are unable to resolve the viral infection and develop chronic hepatitis, which can lead to formation of liver cirrhosis and cancer. To understand better how initial HCV infections progress to chronic liver diseases, we characterised the long term pathogenic effects of HCV infections with the use of a humanised mouse model (HIL mice) we have previously established. Although HCV RNA could be detected in infected mice up to 9 weeks post infection, HCV infected mice developed increased incidences of liver fibrosis, granulomatous inflammation and tumour formation in the form of hepatocellular adenomas or hepatocellular carcinomas by 28 weeks post infection compared to uninfected mice. We also demonstrated that chronic liver inflammation in HCV infected mice was mediated by the human immune system, particularly by monocytes/macrophages and T cells which exhibited exhaustion phenotypes. In conclusion, HIL mice can recapitulate some of the clinical symptoms such as chronic inflammation, immune cell exhaustion and tumorigenesis seen in HCV patients. Our findings also suggest that persistence of HCV-associated liver disease appear to require initial infections of HCV and immune responses but not long term HCV viraemia. © 2017 Zheng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Source Title: PLoS ONE
URI: https://scholarbank.nus.edu.sg/handle/10635/165778
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0184127
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