Fig. 8

Schematic diagram summarizing the pathophysiological scenarios in the cerebellum in the course of SIV infection and antiretroviral treatment. While productive viral replication is undetectable, low-grade microglial activation is seen in the asymptomatic stage of disease (SIV/-AIDS group, subfigure a): tat and gp120 are depicted as presumptive contributors to this process, and granule cell loss is depicted as the result of the collective effects of microglial activation and SIV protein. In the symptomatic stage of disease (SIV/+AIDS group, subfigure b), productive infection is paralleled by high-grade microglial activation, astrogliosis, and macromolecular defects of the BBB resulting in a further loss of granule cells and onset of loss of Purkinje cells. Antiretroviral treatment with the highly CNS-permeant substance 6-Cl-ddG (SIV/+AIDS/+6-Cl-ddG, subfigure c) results in clearance of productive viral infection and restoration of the disintegrated BBB but persistence of low-grade microglial activation and losses of granule cells and Purkinje cells. MNGC multinucleated giant cells, BBB blood brain barrier