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 Han, J.-Y.
Right arrow Articles by Cannon, P. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Han, J.-Y.
Right arrow Articles by Cannon, P. M.

 Previous Article  |  Next Article 

Journal of Virology, November 1998, p. 9101-9108, Vol. 72, No. 11
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Role of Variable Regions A and B in Receptor Binding Domain of Amphotropic Murine Leukemia Virus Envelope Protein

Jin-Young Han, Yi Zhao, W. French Anderson, and Paula M. Cannon*

Gene Therapy Laboratories, Norris Cancer Center and Department of Biochemistry and Molecular Biology, University of Southern California School of Medicine, Los Angeles, California 90033

Received 8 May 1998/Accepted 4 August 1998

For the amphotropic murine leukemia virus (MuLV), a 208-amino-acid amino-terminal fragment of the surface unit (SU) of the envelope glycoprotein is sufficient to bind to its receptor, Pit2. Within this binding domain, two hypervariable regions, VRA and VRB, have been proposed to be important for receptor recognition. In order to specifically locate residues that are important for the interaction with Pit2, we generated a number of site-specific mutations in both VRA and VRB and analyzed the resulting envelope proteins when expressed on retroviral vectors. Concurrently, we substituted portions of the amphotropic SU with homologous regions from the polytropic MuLV envelope protein. The amphotropic SU was unaffected by most of the point mutations we introduced. In addition, the deletion of eight residues in a region of VRA that was previously suggested to be essential for Pit2 utilization only decreased titer on NIH 3T3 cells by 1 order of magnitude. Although the replacement of the amino-terminal two-thirds of VRA with the polytropic sequence abolished receptor binding, smaller nonoverlapping substitutions did not affect the function of the protein. We were not able to identify a single critical receptor contact point within VRA, and we suggest that the amphotropic receptor binding domain probably makes multiple contacts with the receptor and that the loss of some of these contacts can be tolerated.

* Corresponding author. Mailing address: Norris Cancer Center, Rm. 633, University of Southern California School of Medicine, 1441 Eastlake Ave., Los Angeles, CA 90033. Phone: (213) 764-0673. Fax: (213) 764-0097. E-mail: pcannon{at}hsc.usc.edu.

Journal of Virology, November 1998, p. 9101-9108, Vol. 72, No. 11
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Han, J.-Y., Miller, S. A., Wolfe, T. M., Pourhassan, H., Jerome, K. R. (2009). Cell Type-Specific Induction and Inhibition of Apoptosis by Herpes Simplex Virus Type 2 ICP10. J. Virol. 83: 2765-2769 [Abstract] [Full Text]  
  • Abada, P., Noble, B., Cannon, P. M. (2005). Functional Domains within the Human Immunodeficiency Virus Type 2 Envelope Protein Required To Enhance Virus Production. J. Virol. 79: 3627-3638 [Abstract] [Full Text]  
  • Bupp, K., Sarangi, A., Roth, M. J. (2005). Probing Sequence Variation in the Receptor-Targeting Domain of Feline Leukemia Virus Envelope Proteins with Peptide Display Libraries. J. Virol. 79: 1463-1469 [Abstract] [Full Text]  
  • Aguilar, H. C., Anderson, W. F., Cannon, P. M. (2002). Cytoplasmic Tail of Moloney Murine Leukemia Virus Envelope Protein Influences the Conformation of the Extracellular Domain: Implications for Mechanism of Action of the R Peptide. J. Virol. 77: 1281-1291 [Abstract] [Full Text]  
  • Lu, C.-W., O'Reilly, L., Roth, M. J. (2002). G100R Mutation within 4070A Murine Leukemia Virus Env Increases Virus Receptor Binding, Kinetics of Entry, and Viral Transduction Efficiency. J. Virol. 77: 739-743 [Abstract] [Full Text]  
  • Jones, K. S., Nath, M., Petrow-Sadowski, C., Baines, A. C., Dambach, M., Huang, Y., Ruscetti, F. W. (2002). Similar Regulation of Cell Surface Human T-Cell Leukemia Virus Type 1 (HTLV-1) Surface Binding Proteins in Cells Highly and Poorly Transduced by HTLV-1-Pseudotyped Virions. J. Virol. 76: 12723-12734 [Abstract] [Full Text]  
  • Bruett, L., Clements, J. E. (2001). Functional Murine Leukemia Virus Vectors Pseudotyped with the Visna Virus Envelope Show Expanded Visna Virus Cell Tropism. J. Virol. 75: 11464-11473 [Abstract] [Full Text]  
  • Christodoulopoulos, I., Cannon, P. M. (2001). Sequences in the Cytoplasmic Tail of the Gibbon Ape Leukemia Virus Envelope Protein That Prevent Its Incorporation into Lentivirus Vectors. J. Virol. 75: 4129-4138 [Abstract] [Full Text]  
  • Lu, C.-W., Roth, M. J. (2001). Functional Characterization of the N Termini of Murine Leukemia Virus Envelope Proteins. J. Virol. 75: 4357-4366 [Abstract] [Full Text]  
  • Bachrach, E., Marin, M., Pelegrin, M., Karavanas, G., Piechaczyk, M. (2000). Efficient Cell Infection by Moloney Murine Leukemia Virus-Derived Particles Requires Minimal Amounts of Envelope Glycoprotein. J. Virol. 74: 8480-8486 [Abstract] [Full Text]  
  • Tailor, C. S., Nouri, A., Kabat, D. (2000). A Comprehensive Approach to Mapping the Interacting Surfaces of Murine Amphotropic and Feline Subgroup B Leukemia Viruses with Their Cell Surface Receptors. J. Virol. 74: 237-244 [Abstract] [Full Text]  
  • O'Reilly, L., Roth, M. J. (2000). Second-Site Changes Affect Viability of Amphotropic/Ecotropic Chimeric Enveloped Murine Leukemia Viruses. J. Virol. 74: 899-913 [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»