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 Münch, J.
Right arrow Articles by Skowronski, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Münch, J.
Right arrow Articles by Skowronski, J.

 Previous Article  |  Next Article 

Journal of Virology, December 2002, p. 12360-12364, Vol. 76, No. 23
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.23.12360-12364.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

T-Cell Receptor:CD3 Down-Regulation Is a Selected In Vivo Function of Simian Immunodeficiency Virus Nef but Is Not Sufficient for Effective Viral Replication in Rhesus Macaques

Jan Münch,1 Ajit Janardhan,2,3 Nicole Stolte,4 Christiane Stahl-Hennig,4 Peter ten Haaft,5 Jonathan L. Heeney,5 Tomek Swigut,3 Frank Kirchhoff,1* and Jacek Skowronski3*

Abteilung Virologie, Universitätsklinikum, 89081 Ulm, Germany,1 Program in Genetics, State University of New York at Stony Brook, Stony Brook, New York 11794,2 Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724,3 German Primate Center, 37077 Göttingen, Germany,4 Department of Virology, Biomedical Primate Research Center, 2288 GJ Rijswijk, The Netherlands5

Received 8 April 2002/ Accepted 26 August 2002

We investigated the function of severely truncated simian immunodeficiency virus (SIV) Nef proteins (tNef) in vitro and in vivo. These variants emerged in rhesus monkeys infected with SIVmac239 containing a 152-bp deletion in the nef-unique region and have been suggested to enhance SIV virulence (E. T. Sawai, M. S. Hamza, M. Ye, K. E. Shaw, and P. A. Luciw, J. Virol. 74:2038-2045, 2000). We found that the tNef proteins were unable to down-regulate the cell surface expression of major histocompatibility complex class I proteins, CD4, and CD28 and neither stimulated SIV replication nor enhanced virion infectivity. The tNef proteins did efficiently down-regulate T-cell receptor (TCR):CD3 cell surface expression. Nevertheless, the SIVmac239 tnef variants were strongly attenuated in six infected juvenile rhesus macaques. Thus, while the ability of SIV Nef to down-modulate TCR:CD3 cell surface expression apparently confers a selective advantage in vivo, it is insufficient for efficient viral replication in infected macaques. Additional mutations elsewhere in SIVmac239 tnef genomes are required for a virulent phenotype.

* Mailing address for Frank Kirchhoff: Abteilung Virologie-Universit@auml;tsklinikum, Albert-Einstein-Allee 11, 89081 Ulm, Germany. Phone: 49 (731) 50023344. Fax: 49 (731) 50023389. E-mail: frank.kirchhoff{at}medizin.uni-ulm.de.

Corresponding author. Mailing address for Jacek Skowronski: Cold Spring Harbor Laboratory, 1 Bungtown Rd., Cold Spring Harbor, NY 11724. Phone: (516) 367-8407. Fax: (516) 367-8454. E-mail: skowrons{at}cshl.org.

Journal of Virology, December 2002, p. 12360-12364, Vol. 76, No. 23
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.23.12360-12364.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • 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]  
  • Munch, J., Schindler, M., Wildum, S., Rucker, E., Bailer, N., Knoop, V., Novembre, F. J., Kirchhoff, F. (2005). Primary Sooty Mangabey Simian Immunodeficiency Virus and Human Immunodeficiency Virus Type 2 nef Alleles Modulate Cell Surface Expression of Various Human Receptors and Enhance Viral Infectivity and Replication. J. Virol. 79: 10547-10560 [Abstract] [Full Text]  
  • Vigerust, D. J., Egan, B. S., Shepherd, V. L. (2005). HIV-1 Nef mediates post-translational down-regulation and redistribution of the mannose receptor. J. Leukoc. Biol. 77: 522-534 [Abstract] [Full Text]  
  • Schindler, M., Munch, J., Brenner, M., Stahl-Hennig, C., Skowronski, J., Kirchhoff, F. (2004). Comprehensive Analysis of Nef Functions Selected in Simian Immunodeficiency Virus-Infected Macaques. J. Virol. 78: 10588-10597 [Abstract] [Full Text]  
  • Kirchhoff, F., Schindler, M., Bailer, N., Renkema, G. H., Saksela, K., Knoop, V., Muller-Trutwin, M. C., Santiago, M. L., Bibollet-Ruche, F., Dittmar, M. T., Heeney, J. L., Hahn, B. H., Munch, J. (2004). Nef Proteins from Simian Immunodeficiency Virus-Infected Chimpanzees Interact with p21-Activated Kinase 2 and Modulate Cell Surface Expression of Various Human Receptors. J. Virol. 78: 6864-6874 [Abstract] [Full Text]  
  • Eckstein, A K, Quadbeck, B, Tews, S, Mann, K, Kruger, C, Mohr, C H, Steuhl, K-P, Esser, J, Gieseler, R K (2004). Thyroid associated ophthalmopathy: evidence for CD4+ {gamma}{delta} T cells; de novo differentiation of RFD7+ macrophages, but not of RFD1+ dendritic cells; and loss of {gamma}{delta} and {alpha}{beta} T cell receptor expression. Br J Ophthalmol 88: 803-808 [Abstract] [Full Text]  
  • Schindler, M., Wurfl, S., Benaroch, P., Greenough, T. C., Daniels, R., Easterbrook, P., Brenner, M., Munch, J., Kirchhoff, F. (2003). Down-Modulation of Mature Major Histocompatibility Complex Class II and Up-Regulation of Invariant Chain Cell Surface Expression Are Well-Conserved Functions of Human and Simian Immunodeficiency Virus nef Alleles. J. Virol. 77: 10548-10556 [Abstract] [Full Text]  
  • Grivel, J.-C., Santoro, F., Chen, S., Faga, G., Malnati, M. S., Ito, Y., Margolis, L., Lusso, P. (2003). Pathogenic Effects of Human Herpesvirus 6 in Human Lymphoid Tissue Ex Vivo. J. Virol. 77: 8280-8289 [Abstract] [Full Text]  
  • Swigut, T., Greenberg, M., Skowronski, J. (2003). Cooperative Interactions of Simian Immunodeficiency Virus Nef, AP-2, and CD3-{zeta} Mediate the Selective Induction of T-Cell Receptor-CD3 Endocytosis. J. Virol. 77: 8116-8126 [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»