MURINE MODEL FOR MONKEY B VIRUS INFECTION

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DESCRIPTION (provided by applicant): Nonhuman primates (NHPs) are an integral part of biomedical research programs, particularly as animal models of human disease. As long as monkeys are used for research, zoonotic infection by simian viruses will continue to be an occupational hazard. Human infections by BV, a herpes virus of macaques, commonly involve the central nervous system (CNS) and if left untreated, are usually fatal. Even though the first BV case was reported in 1934, there still remain many unanswered questions about BV. A well-characterized small animal model system that could be used to answer such questions does not exist. The goal of this project is to establish and characterize a murine model for BV infection. To achieve this goal, the ID50, CNSD50, and LD50 will be determined for BV infection in the mouse. Histopathology, immunohistochemistry, and immunofluorescence will document the anatomical and temporal spread of virus and viral lesions in the CNS and other tissues. Lesion development and viral localization will also be compared with the temporal development of humoral immunity (ELISA, Western blot), cellular immunity (antigen specific induction of IFN-gamma), and cytokine gene expression (RNAse protection assay) in both the peripheral and the CNS. Following characterization of the murine model, the model will be used to answer the question of whether BV strains isolated from rhesus macaques have greater neuroinvasive and/or neuropathogenicity potential than BV genotypes isolated from other macaque species. Establishment of a well characterized murine model system for BV infection will serve as an important resource in which hypothesis-driven studies can be performed such as evaluation of anti-viral drugs, challenge assessment of potential vaccines, and investigation of the role of various viral genes/proteins in determining the pathogenic properties of these viruses.