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Histopathological and cognitive defects induced by Nef in the brain

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Mordelet, Elodie | Kissa, Karima | Cressant, Arnaud | Gray, Françoise | Ozden, Simona | Vidal, Catherine | Charneau, Pierre | Granon, Sylvie

Edité par CCSD ; Federation of American Society of Experimental Biology -

International audience. 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-alpha, and astrogliosis. No apoptotic event was detected. We further demonstrated that Nef neurotoxicity is associated with cognitive deficits.

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