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 activity against human varicella-zoster virus (VZV) have so far been lacking. Mice 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 monkeys using simian varicella virus (SVV). However, while primates offer potential as models of human varicella disease, their use is limited as experimental 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 demonstrate increasing titres of viral DNA over a 9-day period. In the second model, biocompatible hollow fibres were used for encapsulation of VZV-infected cells. The hollow fibres were then transplanted into immunodeficient and immunocompetent mice and infectious virions were re-isolated. In addition, we demonstrated that both the umbilical cord cushion and the hollow fibre models are suitable tools to test antiviral compounds. Administration of BVDU [brivudine, Helpin, (E)-5-(2-bromovinyl)-2'-deoxyuridine] significantly reduced the VZV titres in both models.