Animal models, such as FIV, are critical to understanding the mechanism of HIV-induced immunodeficiency. The model can be used to dissect the molecular basis of lentivirus-associated immunodeficiency. Preliminary work by the candidate has shown that FIV, like HIV, induces an early and profound deficiency in IL-12 expression, which is associated with susceptibility to T. gondii. What is not yet known is whether this deficiency results from a direct effect of FIV, or whether the virus suppresses critical IL-12 priming cytokines such as TNF(alpha) or IFN(gamma). This application proposes to identify the sequence of protective Type one cytokine suppression. The candidate will also test the hypothesis that exogenous IL-12 administration will reconstitute the cell-mediated immune response, and protect FIV-infected cats from T. gondii challenge. As a veterinary internist and immunologist, Dr. Levy is committed to a career as a clinical investigator in an academic institution. The Co-sponsors of this candidate are authorities in feline retroviral research. The laboratories in which the candidate is engaged are capable of providing the space, equipment, animal facilities, and support staff required for successful completion of the application.
