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 Bültmann, A.
Right arrow Articles by Haas, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bültmann, A.
Right arrow Articles by Haas, J.

 Previous Article  |  Next Article 

Journal of Virology, June 2001, p. 5263-5276, Vol. 75, No. 11
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.11.5263-5276.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Identification of Two Sequences in the Cytoplasmic Tail of the Human Immunodeficiency Virus Type 1 Envelope Glycoprotein That Inhibit Cell Surface Expression

Andreas Bültmann,1 Walter Muranyi,1 Brian Seed,2 and Jürgen Haas1,*

Max von Pettenkofer-Institut, Genzentrum, Ludwig Maximilians Universität München, Munich, Germany,1 and Department of Molecular Biology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 021142

Received 28 April 2000/Accepted 3 March 2001

During synthesis and export of protein, the majority of the human immunodeficiency virus type 1 (HIV-1) Env glycoprotein gp160 is retained in the endoplasmic reticulum (ER) and subsequently ubiquitinated and degraded by proteasomes. Only a small fraction of gp160 appears to be correctly folded and processed and is transported to the cell surface, which makes it difficult to identify negative sequence elements regulating steady-state surface expression of Env at the post-ER level. Moreover, poorly localized mRNA retention sequences inhibiting the nucleocytoplasmic transport of viral transcripts interfere with the identification of these sequence elements. Using two heterologous systems with CD4 or immunoglobulin extracellular/transmembrane domains in combination with the gp160 cytoplasmic domain, we were able to identify two membrane-distal, neighboring motifs, is1 (amino acids 750 to 763) and is2 (amino acids 764 to 785), which inhibited surface expression and induced Golgi localization of the chimeric proteins. To prove that these two elements act similarly in the homologous context of the Env glycoprotein, we generated a synthetic gp160 gene with synonymous codons, the transcripts of which are not retained within the nucleus. In accordance with the results in heterologous systems, an internal deletion of both elements considerably increased surface expression of gp160.

* Corresponding author. Mailing address: Max von Pettenkofer-Institut, Genzentrum, LMU München, Feodor-Lynen-Str. 25, 81377 Munich, Germany. Phone: 49 89 2180 6852. Fax: 49 89 2180 6899. E-mail: haas{at}lmb.uni-muenchen.de.

Journal of Virology, June 2001, p. 5263-5276, Vol. 75, No. 11
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.11.5263-5276.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Gray, E. S., Moore, P. L., Bibollet-Ruche, F., Li, H., Decker, J. M., Meyers, T., Shaw, G. M., Morris, L. (2008). 4E10-Resistant Variants in a Human Immunodeficiency Virus Type 1 Subtype C-Infected Individual with an Anti-Membrane-Proximal External Region-Neutralizing Antibody Response. J. Virol. 82: 2367-2375 [Abstract] [Full Text]  
  • Jiang, J., Aiken, C. (2007). Maturation-Dependent Human Immunodeficiency Virus Type 1 Particle Fusion Requires a Carboxyl-Terminal Region of the gp41 Cytoplasmic Tail. J. Virol. 81: 9999-10008 [Abstract] [Full Text]  
  • Lambele, M., Labrosse, B., Roch, E., Moreau, A., Verrier, B., Barin, F., Roingeard, P., Mammano, F., Brand, D. (2007). Impact of Natural Polymorphism within the gp41 Cytoplasmic Tail of Human Immunodeficiency Virus Type 1 on the Intracellular Distribution of Envelope Glycoproteins and Viral Assembly. J. Virol. 81: 125-140 [Abstract] [Full Text]  
  • Yuste, E., Johnson, W., Pavlakis, G. N., Desrosiers, R. C. (2005). Virion Envelope Content, Infectivity, and Neutralization Sensitivity of Simian Immunodeficiency Virus. J. Virol. 79: 12455-12463 [Abstract] [Full Text]  
  • Beddows, S., Schulke, N., Kirschner, M., Barnes, K., Franti, M., Michael, E., Ketas, T., Sanders, R. W., Maddon, P. J., Olson, W. C., Moore, J. P. (2005). Evaluating the Immunogenicity of a Disulfide-Stabilized, Cleaved, Trimeric Form of the Envelope Glycoprotein Complex of Human Immunodeficiency Virus Type 1. J. Virol. 79: 8812-8827 [Abstract] [Full Text]  
  • Ye, L., Bu, Z., Vzorov, A., Taylor, D., Compans, R. W., Yang, C. (2004). Surface Stability and Immunogenicity of the Human Immunodeficiency Virus Envelope Glycoprotein: Role of the Cytoplasmic Domain. J. Virol. 78: 13409-13419 [Abstract] [Full Text]  
  • Kibler, K. V., Miyazato, A., Yedavalli, V. S. R. K., Dayton, A. I., Jacobs, B. L., Dapolito, G., Kim, S.-j., Jeang, K.-T. (2004). Polyarginine Inhibits gp160 Processing by Furin and Suppresses Productive Human Immunodeficiency Virus Type 1 Infection. J. Biol. Chem. 279: 49055-49063 [Abstract] [Full Text]  
  • Schiavoni, I., Trapp, S., Santarcangelo, A. C., Piacentini, V., Pugliese, K., Baur, A., Federico, M. (2004). HIV-1 Nef Enhances Both Membrane Expression and Virion Incorporation of Env Products: A MODEL FOR THE NEF-DEPENDENT INCREASE OF HIV-1 INFECTIVITY. J. Biol. Chem. 279: 22996-23006 [Abstract] [Full Text]  
  • Day, J. R., Munk, C., Guatelli, J. C. (2004). The Membrane-Proximal Tyrosine-Based Sorting Signal of Human Immunodeficiency Virus Type 1 gp41 Is Required for Optimal Viral Infectivity. J. Virol. 78: 1069-1079 [Abstract] [Full Text]  
  • Blot, G., Janvier, K., Le Panse, S., Benarous, R., Berlioz-Torrent, C. (2003). Targeting of the Human Immunodeficiency Virus Type 1 Envelope to the trans-Golgi Network through Binding to TIP47 Is Required for Env Incorporation into Virions and Infectivity. J. Virol. 77: 6931-6945 [Abstract] [Full Text]  
  • Kalia, V., Sarkar, S., Gupta, P., Montelaro, R. C. (2003). Rational Site-Directed Mutations of the LLP-1 and LLP-2 Lentivirus Lytic Peptide Domains in the Intracytoplasmic Tail of Human Immunodeficiency Virus Type 1 gp41 Indicate Common Functions in Cell-Cell Fusion but Distinct Roles in Virion Envelope Incorporation. J. Virol. 77: 3634-3646 [Abstract] [Full Text]  
  • Venkatesan, S., Petrovic, A., Locati, M., Kim, Y.-O., Weissman, D., Murphy, P. M. (2001). A Membrane-proximal Basic Domain and Cysteine Cluster in the C-terminal Tail of CCR5 Constitute a Bipartite Motif Critical for Cell Surface Expression. J. Biol. Chem. 276: 40133-40145 [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»