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(The FASEB Journal. 2004;18:1851-1861.)
© 2004 FASEB

Histopathological and cognitive defects induced by Nef in the brain

ELODIE MORDELET1, KARIMA KISSA*, ARNAUD CRESSANT{dagger}, FRANCOISE GRAY{ddagger}, SIMONA OZDEN§, CATHERINE VIDAL||, PIERRE CHARNEAU** and SYLVIE GRANON{dagger}{dagger}

Unité Postulante "Mycologie Moléculaire," Institut Pasteur, Paris, France;
* Unité Postulante "Macrophages et Développement de l’Immunité," Institut Pasteur, Paris, France,
{dagger} Unité "Rétrovirus & Transfert génétique," Institut Pasteur, Paris, France;
{ddagger} Service d’Anatomie et de Cytologie Pathologiques, Hôpital Lariboisiere, Paris, France;
§ Unité "Epidémiologie & Physiopathologie des Virus Oncogènes," Institut Pasteur, Paris, France;
|| CEA, Service de Neurologie, CRSSA, EPHE, Fontenay-aux-Roses, France;
** Groupe "Virologie Moléculaire & Vectorologie," Institut Pasteur, Paris, France; and
{dagger}{dagger} Unité "Récepteurs & Cognition," Institut Pasteur, Paris, France

1 Correspondence: Institut Pasteur, 25 rue du Dr. Roux, 75015 Paris, France. E-mail:mordelet{at}pasteur.fr; or granon{at}pasteur.fr

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, 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.


Key Words: neuropathology • behavior • bone marrow-derived macrophages




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