This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
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 arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Hrecka, K.
Right arrow Articles by Skowronski, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hrecka, K.
Right arrow Articles by Skowronski, J.

 Previous Article  |  Next Article 

Journal of Virology, August 2005, p. 10650-10659, Vol. 79, No. 16
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.16.10650-10659.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Nef Proteins from Diverse Groups of Primate Lentiviruses Downmodulate CXCR4 To Inhibit Migration to the Chemokine Stromal Derived Factor 1

Kasia Hrecka,1 Tomek Swigut,1,{dagger} Michael Schindler,2 Frank Kirchhoff,2 and Jacek Skowronski1*

Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724,1 Department of Virology, University of Ulm, 89081 Ulm, Germany2

Received 27 January 2005/ Accepted 20 May 2005

Nef proteins of primate lentiviruses promote viral replication, virion infectivity, and evasion of antiviral immune responses by modulating signal transduction pathways and downregulating expression of receptors at the cell surface that are important for efficient antigen-specific responses, such as CD4, CD28, T-cell antigen receptor, and class I and class II major histocompatibility complex. Here we show that Nef proteins from diverse groups of primate lentiviruses which do not require the chemokine receptor CXCR4 for entry into target cells strongly downmodulate the cell surface expression of CXCR4. In contrast, all human immunodeficiency virus type 1 (HIV-1) and the majority of HIV-2 Nef proteins tested did not have such strong effects. SIVmac239 Nef strongly inhibited lymphocyte migration to CXCR4 ligand, the chemokine stromal derived factor 1 (SDF-1). SIVmac239 Nef downregulated CXCR4 by accelerating the rate of its endocytosis. Downmodulation of CXCR4 was abolished by mutations that disrupt the constitutively strong AP-2 clathrin adaptor binding element located in the N-terminal region of the Nef molecule, suggesting that Nef accelerates CXCR4 endocytosis via an AP-2-dependent pathway. Together, these results point to CXCR4 as playing an important role in simian immunodeficiency virus and possibly also HIV-2 persistence in vivo that is unrelated to viral entry into target cells. We speculate that Nef targets CXCR4 to disrupt ordered trafficking of infected leukocytes between local microenvironments in order to facilitate their dissemination and/or impair the antiviral immune response.

* Corresponding author. Mailing address: Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724. Phone: 516 367 8407. Fax: 516 367 8407. E-mail: skowrons{at}cshl.org.

{dagger} Present address: The Rockefeller University, New York, NY 10021.

Journal of Virology, August 2005, p. 10650-10659, Vol. 79, No. 16
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.16.10650-10659.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Laguette, N., Benichou, S., Basmaciogullari, S. (2009). Human Immunodeficiency Virus Type 1 Nef Incorporation into Virions Does Not Increase Infectivity. J. Virol. 83: 1093-1104 [Abstract] [Full Text]  
  • Munch, J., Rajan, D., Schindler, M., Specht, A., Rucker, E., Novembre, F. J., Nerrienet, E., Muller-Trutwin, M. C., Peeters, M., Hahn, B. H., Kirchhoff, F. (2007). Nef-Mediated Enhancement of Virion Infectivity and Stimulation of Viral Replication Are Fundamental Properties of Primate Lentiviruses. J. Virol. 81: 13852-13864 [Abstract] [Full Text]  
  • Venzke, S., Michel, N., Allespach, I., Fackler, O. T., Keppler, O. T. (2006). Expression of Nef Downregulates CXCR4, the Major Coreceptor of Human Immunodeficiency Virus, from the Surfaces of Target Cells and Thereby Enhances Resistance to Superinfection. J. Virol. 80: 11141-11152 [Abstract] [Full Text]  
  • Wildum, S., Schindler, M., Munch, J., Kirchhoff, F. (2006). Contribution of vpu, env, and nef to CD4 down-modulation and resistance of human immunodeficiency virus type 1-infected T cells to superinfection.. J. Virol. 80: 8047-8059 [Abstract] [Full Text]  
  • Michel, N., Ganter, K., Venzke, S., Bitzegeio, J., Fackler, O. T., Keppler, O. T. (2006). The Nef Protein of Human Immunodeficiency Virus Is a Broad-Spectrum Modulator of Chemokine Receptor Cell Surface Levels That Acts Independently of Classical Motifs for Receptor Endocytosis and G{alpha}i Signaling. Mol. Biol. Cell 17: 3578-3590 [Abstract] [Full Text]  
  • Brenner, M., Munch, J., Schindler, M., Wildum, S., Stolte, N., Stahl-Hennig, C., Fuchs, D., Matz-Rensing, K., Franz, M., Heeney, J., Ten Haaft, P., Swigut, T., Hrecka, K., Skowronski, J., Kirchhoff, F. (2006). Importance of the N-Distal AP-2 Binding Element in Nef for Simian Immunodeficiency Virus Replication and Pathogenicity in Rhesus Macaques. J. Virol. 80: 4469-4481 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»