spacer gif spacer gif spacer gif spacer gif spacer gif
QUICK SEARCH:   [advanced]


spacer gif
     Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents    

First published online 17 October 2006
doi: 10.1242/jcs.03231

Journal of Cell Science 119, 4520-4530 (2006)
Published by The Company of Biologists 2006
This Article
Right arrow Figures Only
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
jcs.03231v1
119/21/4520    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Lehmann, M. H.
Right arrow Articles by Erfle, V.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lehmann, M. H.
Right arrow Articles by Erfle, V.

Research Article

HIV-1 Nef upregulates CCL2/MCP-1 expression in astrocytes in a myristoylation- and calmodulin-dependent manner

Michael H. Lehmann1,2,*, Sabine Masanetz1,2, Susanne Kramer1 and Volker Erfle1,2

1 Institute of Molecular Virology, GSF-National Research Center for Environment and Health, Ingolstädter Landstr. 1, 85764 Neuherberg, Germany
2 Institute of Virology, Technical University of Munich, Schneckenburgerstr. 8, 81675 Munich, Germany

* Author for correspondence (e-mail: orlataler{at}web.de)

Accepted 22 August 2006

HIV-associated dementia (HAD) correlates with infiltration of monocytes into the brain. The accessory HIV-1 negative factor (Nef) protein, which modulates several signaling pathways, is constitutively present in persistently infected astroctyes. We demonstrated that monocytes responded with chemotaxis when subjected to cell culture supernatants of nef-expressing astrocytic U251MG cells. Using a protein array, we identified CC chemokine ligand 2/monocyte chemotactic protein-1 (CCL2/MCP-1) as a potential chemotactic factor mediating this phenomenon. CCL2/MCP-1 upregulation by Nef was further confirmed by ribonuclease protection assay, RT-PCR and ELISA. By applying neutralizing antibodies against CCL2/MCP-1 and using CCR2-deficient monocytes, we confirmed CCL2/MCP-1 as the exclusive factor secreted by nef-expressing astrocytes capable of attracting monocytes. Additionally, we showed that Nef-induced CCL2/MCP-1 expression depends on the myristoylation moiety of Nef and requires functional calmodulin. In summary, we suggest that Nef-induced CCL2/MCP-1 expression in astrocytes contributes to infiltration of monocytes into the brain, and thereby to progression of HAD.

Key words: AIDS, Calmodulin, Chemotaxis, Dementia, Myristoylation




This article has been cited by other articles:


Home page
 FASEB J.Home page
D. Hoffmann, J. Seebach, A. Cosma, F. D. Goebel, K. Strimmer, H. M. Schatzl, and V. Erfle
Therapeutic vaccination reduces HIV sequence variability
FASEB J, February 1, 2008; 22(2): 437 - 444.
[Abstract] [Full Text] [PDF]


© The Company of Biologists Ltd 2006