The DOI matches its Crossref record; 2 of the 2 references it cites were found in a registry or an index.
A Humanized Mouse Model to Study Hepatitis C Virus Infection, Immune Response, and Liver Disease
Open accessAbstract
Background & Aims Studies of hepatitis C virus (HCV) infection, immunopathogenesis, and resulting liver diseases have been hampered by the lack of a small animal model. We developed humanized mice with human immune system and liver tissues to improve the studies of hepatitis C pathogenesis and treatment. Methods To promote engraftment of human hepatocytes, we expressed a fusion protein of the FK506 binding protein (FKBP) and caspase 8 under control of the albumin promoter (AFC8), which induces liver cell death, in Balb/C Rag2-/- γC-null mice. Co-transplantation of human CD34+ human hematopoietic stem cells (HSC) and hepatocyte progenitors into the transgenic mice led to efficient engraftment of human leukocytes and hepatocytes. We then infected these humanized mice (AFC8-hu HSC/Hep) with primary HCV isolates and studied HCV-induced immune responses and liver diseases. Results HCV-infected livers of AFC8-hu HSC/Hep mice generated a human immune T-cell response against HCV. HCV infection induced liver inflammation, hepatitis, and fibrosis, which correlated with activation of stellate cells and expression of human fibrogenic genes. Conclusions AFC8-hu HSC/Hep mice are a useful model of HCV infection, the immune response, and liver disease, because they contain human immune system and liver cells. These mice become infected with HCV, generate a specific immune response against the virus, and develop liver diseases that include hepatitis and fibrosis. This model might also be used to develop therapeutics for HCV infection.
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Cites
Hepatic T cells and liver tolerance
Crispe, I. N. (2003) · Nature Reviews Immunology · doi:10.1038/nri981 · Cited by 661
Pajvani, U. B., Trujillo, M. E., Combs, T. P., Iyengar, P., Jelicks, L., Roth, K. A., Kitsis, R. N., & Scherer, P. E. (2005) · Nature Medicine · doi:10.1038/nm1262 · Cited by 322
Cited by
Current advances in humanized mouse models
Ito, R., Takahashi, T., Katano, I., & Ito, M. (2012) · Cellular & Molecular Immunology · doi:10.1038/cmi.2012.2 · Cited by 349
Bility, M. T., Cheng, L., Zhang, Z., Luan, Y., Li, F., Chi, L., Zhang, L., Tu, Z., Gao, Y., Fu, Y., et al. (2014) · PLoS Pathogens · doi:10.1371/journal.ppat.1004032 · Cited by 227
Self-citationBillerbeck, E., Mommersteeg, M. C., Shlomai, A., Xiao, J. W., Andrus, L., Bhatta, A., Vercauteren, K., Michailidis, E., Dorner, M., Krishnan, A., et al. (2016) · Journal of Hepatology · doi:10.1016/j.jhep.2016.04.022 · Cited by 87
Self-citationChronic hepatitis C infection–induced liver fibrogenesis is associated with M2 macrophage activation
Bility, M. T., Nio, K., Li, F., McGivern, D. R., Lemon, S. M., Feeney, E. R., Chung, R. T., & Su, L. (2016) · Scientific Reports · doi:10.1038/srep39520 · Cited by 71
Self-citationPreclinical models of idiosyncratic drug-induced liver injury (iDILI): Moving towards prediction
Segovia-Zafra, A., Di Zeo-Sánchez, D. E., López-Gómez, C., Pérez-Valdés, Z., García-Fuentes, E., Andrade, R. J., Lucena, M. I., & Villanueva-Paz, M. (2021) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2021.11.013 · Cited by 70
Metadata
- Authors
- Washburn, M. L., Bility, M. T., Zhang, L., Kovalev, G. I., Buntzman, A., Frelinger, J. A., Barry, W., Ploss, A., Rice, C. M., & Su, L.
- Venue
- Gastroenterology
- Publisher
- Elsevier BV
- Published
- 2011-04
- Volume
- 140
- Issue
- 4
- Pages
- 1334-1344
- ISSN
- 0016-5085 (ISSN-L)
- OpenAlex
- W2100943457
- Cited by
- 316
- References
- 2
- FWCI
- 23.02
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Washburn, M. L., Bility, M. T., Zhang, L., Kovalev, G. I., Buntzman, A., Frelinger, J. A., Barry, W., Ploss, A., Rice, C. M., & Su, L. (2011). A Humanized Mouse Model to Study Hepatitis C Virus Infection, Immune Response, and Liver Disease. Gastroenterology. https://doi.org/10.1053/j.gastro.2011.01.001
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