HCV's mighty mouse
The most widely used animal model of HCV infection requires transplanting human hepatocytes into immunodeficient mice. These mice are useful for testing antivirals, but the absence of an immune system makes the animals unsuitable for studying other classes of HCV products such as vaccines and immunotherapeutics. Now, researchers from The Rockefeller University have developed an immunocompetent, genetically humanized mouse that allows limited HCV infection, albeit not replication.1
The researchers are in discussions with an undisclosed company interested in exclusivelylicensing the technology to evaluate HCV entry inhibitors and vaccines.
The Rockefeller group used a two-pronged approach to develop the model: genetically humanizing the mice with human HCV entry factors and infecting the animals with a sensitive HCV luciferase reporter system.
First, the researchers intravenously delivered adenovirus vectors encoding human host entry factors CD81, scavenger receptor class B member 1 (SCARB1), claudin 1 (CLDN1) and/or occludin (OCLN) to mice. About 18%-25% of murine hepatocytes had strong expression of human CD81 and OCLN, and all 4 proteins showed up in about 5% of murine hepatocytes.
To detect HCV infection in the liver, mice were engineered to express the luciferase gene following inoculation with HCV.
The signal peaked at