Histopathological and cognitive defects induced by Nef in the brain.

Complex mechanisms of human immunodeficiency virus type-1 (HIV-1) brain pathogenesis suggest the contribution of individual HIV-1 gene products. Among them, the Nef protein has been reported to harbor a major determinant of pathogenicity in AIDS-like disease. The goal of the present study was to determine whether Nef protein expressed in vivo by primary macrophages could induce a brain toxicity also affecting the behavior of the rat. To achieve this goal we grafted Nef-transduced macrophages into the rat hippocampus. Two months post-transplantation, we observed that Nef induces monocyte/macrophage recruitment, expression of TNF-α, and astrogliosis. No apoptotic event was detected. We further demonstrated that Nef neurotoxicity is associated with cognitive deficits.--Mordelet, E., Kissa, K., Cressant, A., Gray, F., Ozden, S., Vidal, C., Charneau, P., Granon, S. Histopathological and cognitive defects induced by Nef in the brain. [ABSTRACT FROM AUTHOR]