In HIV associated neurological disease (HAND), HIV infected macrophages- and Fcgamma receptor III (CD16) positive macrophages and monocytes in particular, have been associated with disease pathogenesis. However, the differences between normal CD16+ monocytes that appear to have a role in replenishing tissue macrophages and dysfunctional CD16+ monocytes that appear to foster inflammation are not well defined. Pathologica LLC has recently developed a very sensitive molecular assay for the detection of the dysfunctional macrophage subset associated with severe neurodegenerative disease and by inference HIV associated neurological disease. In this program project grant all of the research proposals will make extensive use of this assay in the course of their investigations. Accordingly performance of this multi-gene real time quantitative reverse-transcription-PCR assay will be centralized at Pathologica during the course of this program project. Additionally, Pathologica will provide quantitative HIV and SIV PCR assays for all sites, including HIV proviral load, SIV proviral load, and SIV RNA. These assays will allow for an unambiguous determination if treatment with polyamine biosynthesis inhibitors significantly impacts HIV or SIV replication. The performance of these HIV / SIV assays at one location will help ensure the reproducibility and quality of the assay data for all research projects, as well as results in some cost savings.
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