The Chimpanzee Model of Hepatitis C Infections and Small Animal Surrogates
Robert E. Lanford, Stanley M. Lemon and Christopher Walker
from: Hepatitis C: Antiviral Drug Discovery and Development (Edited by: Seng-Lai Tan and Yupeng He). Caister Academic Press, U.K. (2011)
The chimpanzee model of HCV infection has been instrumental in many of the key advances in HCV research and therapy. The demonstration of an infectious agent for NonA,NonB hepatitis, the propensity for persistent infections, and the physical properties of the virus were all determined in the chimpanzee prior to the isolation of HCV. The cloning of HCV was dependent on high titer chimpanzee plasma, and the verification of infectious clones could be accomplished only in this animal model. Immunological analyses in HCV infected chimpanzees have been essential in defining the immune correlates of viral clearance and the failed immune response in persistent infections. The chimpanzee is the only animal suitable for vaccine development, and the knowledge gained from chimpanzee studies has brought us closer to that realization. Analysis of hepatic gene expression in the chimpanzee has revealed signature changes in the innate immune response to HCV and the basis for the lack of response to IFN in null responders. Chimpanzees are often the last stage of preclinical development for antivirals and new therapeutics progressing to human trials. Although the chimpanzee is indispensible for many studies, the marmoset model of GBV-B infection and immunodeficient mice with mouse/human chimeric livers are important surrogate models. The identification of HCV receptors and many host factors essential for replication suggest that the future may hold a mouse fully susceptible to HCV infection read more ...