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-alpha, and astrogliosis. No apoptotic event was detected. We further demonstrated that Nef neurotoxicity is associated with cognitive deficits.
Mordelet
Elodie
E
Unité Postulante "Mycologie Moléculaire," Institut Pasteur, Paris, France. mordelet@pasteur.fr
Kissa
Karima
K
Cressant
Arnaud
A
Gray
Francoise
F
Ozden
Simona
S
Vidal
Catherine
C
Charneau
Pierre
P
Granon
Sylvie
S
D000818:Animals; D001522:Behavior, Animal; D001854:Bone Marrow Cells / Q000166:cytology; D002478:Cells, Cultured; D002633:Chemotaxis; D003072:Cognition Disorders / Q000473:pathology / Q000523:psychology / Q000821:virology*; D015693:Gene Products, nef / Q000235:genetics / Q000378:metabolism*; D015658:HIV Infections / Q000473:pathology* / Q000821:virology; D006624:Hippocampus / Q000166:cytology / Q000473:pathology* / Q000821:virology; D008264:Macrophages / Q000637:transplantation / Q000821:virology; D008297:Male; D051381:Rats; D020318:Rats, Long-Evans; D014161:Transduction, Genetic; D054311:nef Gene Products, Human Immunodeficiency Virus
D015693:Gene Products, nef; D054311:nef Gene Products, Human Immunodeficiency Virus