A MONKEY MODEL FOR ANTI-CYTOMEGALOVIRUS THERAPY

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. Objective: The long-range goal of this project is to develop a non-human primate model to evaluate therapy for human cytomegalovirus (HCMV) that will 1) enable rapid in vivo evaluation of promising anti-HCMV drugs and 2) allow development of therapeutic strategies for HCMV under clinically relevant conditions. For these studies we are using Rhesus CMV (RhCMV) infection of rhesus macaques. We have previously established with in vitro studies that RhCMV and HCMV are nearly identical in susceptibility to the drugs that are approved for HCMV therapy in humans. In the past year we have evaluated the FDA approved drug cidofovir (CDV) for anti-RhCMV activity in macaques during acute infection. A pharmokinetics study was performed to establish an appropriate dose and route of CDV administration. The optimal dose was 5 mg/kg given intraveneously, once weekly, which is equivalent to the CDV dose used for HCMV therapy in humans. Ten RhCMV-infected macaques were treated with CDV and compared to ten mock-treated controls. Virus loads in the treated animals were reduced more than 99% relative to mock-treated controls. These studies validate the RhCMV model for in vivo studies of HCMV therapy.