Novel mouse models for the investigation of experimental drugs with activity against human varicella-zoster virus

Suitable small animal models for the testing of antiviral agents with activ ity against human varicella-zoster virus (VZV) have so far been lacking. Mi ce and other animals have been found to not be susceptible to VZV infection . The model of choice for drug development has been the infection of monkey s using simian varicella virus (SVV). However, while primates offer potenti al as models of human varicella disease, their use is limited as experiment al models in antiviral research. We have developed two simple mouse models that support replication of human VZV in vivo. In the first, SCID mice were transplanted with human umbilical cord (umbilical cord cushion model) and subsequently infected with VZV. After infection, we were able to demonstrat e increasing titres of viral DNA over a 9-day period. In the second model, biocompatible hollow fibres were used for encapsulation of VZV-infected cel ls. The hollow fibres were then transplanted into immunodeficient and immun ocompetent mice and infectious virions were re-isolated. In addition, we de monstrated that both the umbilical cord cushion and the hollow fibre models are suitable tools to test antiviral compounds. Administration of BVDU [br ivudine, Helpin, (E)-5-(2-bromovinyl)-2'-deoxyuridine] significantly reduce d the VZV titres in both models.