TLR LIGANDS IN GBV-B

这个子项目是众多研究子项目之一

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. GBV-B virus is the virus most closely related to human hepatitis C virus and it causes hepatitis in marmosets. Thus, this is a small animal surrogate for HCV. The use of this model reduces the use of chimpanzees in HCV studies, since chimpanzees are the only animal other than man that can. be infected with HCV. In this study, we will examine an antiviral compound developed to treat chronic HCV infection for antiviral properties in the GBV-B infected marmoset. The compound has immune modulation properties that are expected to induce an innate immune response including IFN. The compound has been tested for safety and induction of innate immune response in cynomolgus monkeys. Prior to progressing to clinical trials, the compound needs to be tested in vivo for the ability to inhibit viral replication in the liver of a suitable animal model for HCV. The nature of the compound is such that it is expected to be equally effective against GBV-B and HCV. Due to the lack of response to IFN in HCV chronically infected chimpanzees, the HCV infected chimpanzee is not a suitable model for the testing of this compound. The study will use 12 marmosets. In the PK phase, the animals will be given a single oral dose by gavage (6 animals) or with an oral treat. Blood samples will be taken twice over 24 hrs. The animals will be rested for 30 days prior to the efficacy phase. In the efficacy phase, animals will be infected with GBV-B and then given 15 oral doses of compound, every other day for 30 days. The level of virus will be monitored in the blood before, during and after drug administration for a period of 20 weeks. The animals will be divided into 3 groups, low dose, high dose and no drug. The animals will be monitored closely for adverse events including complete blood counts and blood chemistries.