HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Koedel, U. Articles by Pfister, H.-W. Search for Related Content PubMed PubMed Citation Articles by Koedel, U. Articles by Pfister, H.-W.

HIV Type 1 Nef Protein Is a Viral Factor for Leukocyte Recruitment into the Central Nervous System¹

Uwe Koedel^*, Birgit Kohleisen, Bernd Sporer^*, Fritz Lahrtz, Vladimir Ovod, Adriano Fontana, Volker Erfle and Hans-Walter Pfister^2,*

^* Department of Neurology, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, Munich, Germany; Institute of Molecular Virology, GSF-Research Center for Environment and Health Neuherberg, Neuherberg; Germany, Institute of Biomedical Sciences, University of Tampere, Tampere, Finland; and Institute of Clinical Immunology, University Hospital Zürich, Zürich, Switzerland

Recombinant HIV-1 Nef protein, but not Tat, gp120, and gp160, provoked leukocyte recruitment into the CNS in a rat model. The strong reduction of bioactivity by heat treatment of Nef, and the blocking effect of the mAb 2H12, which recognizes the carboxy-terminal amino acid (aa) residues 171–190 (but not of mAb 3E6, an anti-Nef Ab of the same isotype, which maps the aa sequence 168–175, as well as a mixture of mAbs to CD4) provided evidence for the specificity of the observed Nef effects. Using a modified Boyden chamber technique, Nef exhibited chemotactic activity on mononuclear cells in vitro. Coadministration of the anti-Nef mAb 2H12, as well as treatment of Nef by heat inhibited Nef-induced chemotaxis. Besides soluble Nef, chemotaxis was also induced by a Nef-expressing human astrocytoma cell line, but not by control cells. These data suggest a direct chemotactic activity of soluble Nef. The detection of elevated levels of IL-6, TNF-, and IFN- in rat cerebrospinal fluid 6 h after intracisternal Nef injection hint at the additional involvement of indirect mechanisms in Nef-induced leukocyte migration into rat CNS. These data propose a mechanism by which HIV-1 Nef protein may be essential for AIDS neuropathogenesis, as a mediator of the recruitment of leukocytes that may serve as vehicles of the virus and perpetrators for disease through their production of neurotoxins.