The short term goal of this proposal is to establish a new, novel, and convenient small animal model that will be important for further research into the etiology of HIV neuropathology, and valuable for testing drug candidates against HIV-induced CNS disease. We propose to use new and powerful gene vectors derived from Adeno Associated virus (AAV) to transfer individual HIV genes in a targeted manner into microglia and macrophages in the rat brain, the same cell types which are susceptible to HIV in natural infections. In vivo characterization of the expression and effects of the delivered gene products will allow us to fully evaluate the utility of this approach to model different aspects of HIV-associated neuropathology. In this pilot proposal, we will establish a proof of principle of this approach, generating animals stably expressing individual HIV products relevant to pathology in their microglia, and characterizing their expression with respect to dispersal, cell type specificity, and persistence. Once established, further work can be performed to analyze particular pathologies, and their molecular mechanisms, in these animals.
| Cucchiarini, M; Ren, X L; Perides, G et al. (2003) Selective gene expression in brain microglia mediated via adeno-associated virus type 2 and type 5 vectors. Gene Ther 10:657-67 |
