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 Liu, L. X.
Right arrow Articles by Benarous, R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Liu, L. X.
Right arrow Articles by Benarous, R.

 Previous Article  |  Next Article 

Journal of Virology, June 2000, p. 5310-5319, Vol. 74, No. 11
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Mutation of a Conserved Residue (D123) Required for Oligomerization of Human Immunodeficiency Virus Type 1 Nef Protein Abolishes Interaction with Human Thioesterase and Results in Impairment of Nef Biological Functions

Lang Xia Liu,1 Nikolaus Heveker,2 Oliver T. Fackler,3 Stefan Arold,4 Sylvie Le Gall,5 Katy Janvier,1 B. Matija Peterlin,3 Christian Dumas,4 Olivier Schwartz,5 Serge Benichou,1 and Richard Benarous1,*

Institut Cochin de Génétique Moléculaire, INSERM U 529 Université Paris V,1 and INSERM U 332,2 75014 Paris, Centre de Biochimie Structurale, UMR 9955 CNRS U414 INSERM, 34060 Montpellier,4 and Laboratoire Rétrovirus et Transfert Génétique, URA CNRS 1157, Institut Pasteur, 75724 Paris Cedex 15,5 France, and Howard Hughes Medical Institute and Departments of Medicine, Microbiology, and Immunology, University of California at San Francisco, San Francisco, California 94143-07033

Received 24 November 1999/Accepted 2 March 2000

Nef is a myristoylated protein of 27 to 35 kDa that is conserved in primate lentiviruses. In vivo, Nef is required for high viral load and full pathological effects. In vitro, Nef has at least four activities: induction of CD4 and major histocompatibility complex (MHC) class I downregulation, enhancement of viral infectivity, and alteration of T-cell activation pathways. We previously reported that the Nef protein from human immunodeficiency virus type 1 interacts with a novel human thioesterase (hTE). In the present study, by mutational analysis, we identified a region of the Nef core, extending from the residues D108 to W124, that is involved both in Nef-hTE interaction and in Nef-induced CD4 downregulation. This region of Nef is located on the oligomer interface and is in close proximity to the putative CD4 binding site. One of the mutants carrying a mutation in this region, targeted to the conserved residue D123, was also found to be defective in two other functions of Nef, MHC class I downmodulation and enhancement of viral infectivity. Furthermore, mutation of this residue affected the ability of Nef to form dimers, suggesting that the oligomerization of Nef may be critical for its multiple functions.

* Corresponding author. Mailing address: Interactions Moléculaires Hôte-Pathogène, INSERM U 529, ICGM, 24, Rue du Faubourg Saint-Jacques, 75014 Paris, France. Phone: (33) 1 44 41 25 65. Fax: (33) 1 44 41 23 99. E-mail: benarous{at}cochin.inserm.fr.

Journal of Virology, June 2000, p. 5310-5319, Vol. 74, No. 11
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Chaudhuri, R., Mattera, R., Lindwasser, O. W., Robinson, M. S., Bonifacino, J. S. (2009). A Basic Patch on {alpha}-Adaptin Is Required for Binding of Human Immunodeficiency Virus Type 1 Nef and Cooperative Assembly of a CD4-Nef-AP-2 Complex. J. Virol. 83: 2518-2530 [Abstract] [Full Text]  
  • Lu, T.-c., He, J. C., Wang, Z.-h., Feng, X., Fukumi-Tominaga, T., Chen, N., Xu, J., Iyengar, R., Klotman, P. E. (2008). HIV-1 Nef Disrupts the Podocyte Actin Cytoskeleton by Interacting with Diaphanous Interacting Protein. J. Biol. Chem. 283: 8173-8182 [Abstract] [Full Text]  
  • Wonderlich, E. R., Williams, M., Collins, K. L. (2008). The Tyrosine Binding Pocket in the Adaptor Protein 1 (AP-1) {micro}1 Subunit Is Necessary for Nef to Recruit AP-1 to the Major Histocompatibility Complex Class I Cytoplasmic Tail. J. Biol. Chem. 283: 3011-3022 [Abstract] [Full Text]  
  • Pizzato, M., Helander, A., Popova, E., Calistri, A., Zamborlini, A., Palu, G., Gottlinger, H. G. (2007). Dynamin 2 is required for the enhancement of HIV-1 infectivity by Nef. Proc. Natl. Acad. Sci. USA 104: 6812-6817 [Abstract] [Full Text]  
  • Crotti, A., Neri, F., Corti, D., Ghezzi, S., Heltai, S., Baur, A., Poli, G., Santagostino, E., Vicenzi, E. (2006). Nef Alleles from Human Immunodeficiency Virus Type 1-Infected Long-Term-Nonprogressor Hemophiliacs with or without Late Disease Progression Are Defective in Enhancing Virus Replication and CD4 Down-Regulation. J. Virol. 80: 10663-10674 [Abstract] [Full Text]  
  • Vincent, P., Priceputu, E., Kay, D., Saksela, K., Jolicoeur, P., Hanna, Z. (2006). Activation of p21-activated Kinase 2 and Its Association with Nef Are Conserved in Murine Cells but Are Not Sufficient to Induce an AIDS-like Disease in CD4C/HIV Transgenic Mice. J. Biol. Chem. 281: 6940-6954 [Abstract] [Full Text]  
  • O'Neill, E., Kuo, L. S., Krisko, J. F., Tomchick, D. R., Garcia, J. V., Foster, J. L. (2006). Dynamic Evolution of the Human Immunodeficiency Virus Type 1 Pathogenic Factor, Nef. J. Virol. 80: 1311-1320 [Abstract] [Full Text]  
  • Cluet, D., Bertsch, C., Beyer, C., Gloeckler, L., Erhardt, M., Gut, J.-P., Galzi, J.-L., Aubertin, A.-M. (2005). Detection of Human Immunodeficiency Virus Type 1 Nef and CD4 Physical Interaction in Living Human Cells by Using Bioluminescence Resonance Energy Transfer. J. Virol. 79: 8629-8636 [Abstract] [Full Text]  
  • Madrid, R., Janvier, K., Hitchin, D., Day, J., Coleman, S., Noviello, C., Bouchet, J., Benmerah, A., Guatelli, J., Benichou, S. (2005). Nef-induced Alteration of the Early/Recycling Endosomal Compartment Correlates with Enhancement of HIV-1 Infectivity. J. Biol. Chem. 280: 5032-5044 [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]  
  • Alexander, M., Bor, Y.-c., Ravichandran, K. S., Hammarskjold, M.-L., Rekosh, D. (2004). Human Immunodeficiency Virus Type 1 Nef Associates with Lipid Rafts To Downmodulate Cell Surface CD4 and Class I Major Histocompatibility Complex Expression and To Increase Viral Infectivity. J. Virol. 78: 1685-1696 [Abstract] [Full Text]  
  • Stove, V., Naessens, E., Stove, C., Swigut, T., Plum, J., Verhasselt, B. (2003). Signaling but not trafficking function of HIV-1 protein Nef is essential for Nef-induced defects in human intrathymic T-cell development. Blood 102: 2925-2932 [Abstract] [Full Text]  
  • Williams, M., Roeth, J. F., Kasper, M. R., Fleis, R. I., Przybycin, C. G., Collins, K. L. (2002). Direct Binding of Human Immunodeficiency Virus Type 1 Nef to the Major Histocompatibility Complex Class I (MHC-I) Cytoplasmic Tail Disrupts MHC-I Trafficking. J. Virol. 76: 12173-12184 [Abstract] [Full Text]  
  • Lundquist, C. A., Tobiume, M., Zhou, J., Unutmaz, D., Aiken, C. (2002). Nef-Mediated Downregulation of CD4 Enhances Human Immunodeficiency Virus Type 1 Replication in Primary T Lymphocytes. J. Virol. 76: 4625-4633 [Abstract] [Full Text]  
  • Janvier, K., Craig, H., Le Gall, S., Benarous, R., Guatelli, J., Schwartz, O., Benichou, S. (2001). Nef-Induced CD4 Downregulation: a Diacidic Sequence in Human Immunodeficiency Virus Type 1 Nef Does Not Function as a Protein Sorting Motif through Direct Binding to {beta}-COP. J. Virol. 75: 3971-3976 [Abstract] [Full Text]  
  • Manninen, A., Huotari, P., Hiipakka, M., Renkema, G. H., Saksela, K. (2001). Activation of NFAT-Dependent Gene Expression by Nef: Conservation among Divergent Nef Alleles, Dependence on SH3 Binding and Membrane Association, and Cooperation with Protein Kinase C-{theta}. J. Virol. 75: 3034-3037 [Abstract] [Full Text]  
  • Doms, R. W., Trono, D. (2000). The plasma membrane as a combat zone in the HIV battlefield. Genes Dev. 14: 2677-2688 [Full Text]  
  • Yang, S., Sun, Y., Zhang, H. (2001). The Multimerization of Human Immunodeficiency Virus Type I Vif Protein. A REQUIREMENT FOR Vif FUNCTION IN THE VIRAL LIFE CYCLE. J. Biol. Chem. 276: 4889-4893 [Abstract] [Full Text]  
  • Hunt, M. C., Solaas, K., Kase, B. F., Alexson, S. E. H. (2002). Characterization of an Acyl-CoA Thioesterase That Functions as a Major Regulator of Peroxisomal Lipid Metabolism. J. Biol. Chem. 277: 1128-1138 [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»