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Nomenclature
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AFC8-HSC/Hep Balb/C Rag2−/−γC−/−
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NOD/scid-DRB*0101 |
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Engraftment method for humanization of immune system
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Intrahepatic injection |
Intrahepatic injection |
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Engraftment method for humanization of liver
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Intrahepatic injection |
Intrahepatic injection |
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Source of cells
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Human adult cells |
Human fetal liver |
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Presence of human hepatocytes
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Yes |
Yes |
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Presence of human immune system
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Yes |
Yes |
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Method of HCV infection
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Intravenous injection |
Intravenous injection |
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Strain of HCV used
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Clinical isolate of HCV genotype 1a (1-5 x 107 genome copies/mL) |
Recombinant adenovirus serotype 5 (AdV5) (5 x 109 or 1010 particles) |
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Duration monitored post-HCV infection
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Up to 20 weeks |
Up to 4 weeks |
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Advantages
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The use of caspase 8-dependent induction of mouse hepatocyte apoptosis to promote human hepatocyte repopulation is less toxic as compared with uPA/SCID and FAH mice Presence of both human immune system and hepatocytes AFC8-hu HSC/Hep mice infected with HCV generates human immune responses, elevated levels of alanine aminotransferase (ALT), liver inflammation, hepatitis and fibrosis Suitable for the study of hepatitis virus-induced liver immunopathogenesis HCV genomic RNA is detectable in the livers of mice Only small animal model capable to support the co-infection of HCV and HIV Useful platform for the evaluation of antiviral drugs and immunotherapies
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Presence of both human immune system and hepatocytes Transgenic HLA expression improves human antiviral HLA-restricted T cell responses during human viral infections Suitable for the study of hepatitis virus-induced liver immunopathogenesis
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Drawbacks
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Liver sinusoidal endothelium is of mouse origin Low level of repopulation and immature phenotype of human hepatocytes Unable to detect significant HCV viremia in the blood Low serum levels of human albumin and HCV viremia Cannot be used for long-term studies Antiviral immune responses may not be as robust as in human patients Does not fully recapitulate clinical settings
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To analyze HCV immunopathogenesis, mice must be engrafted with both donor matched human hepatocytes and immune cells, hence making this a challenging model to establish Liver sinusoidal endothelium is of mouse origin Lack of complete viral clearance from the liver Does not fully recapitulate clinical settings
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References
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