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
Right arrow Citation Map
Services
Right arrow E-mail this article to a friend
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 Barnett, A. L.
Right arrow Articles by Cunningham, J. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Barnett, A. L.
Right arrow Articles by Cunningham, J. M.

 Previous Article  |  Next Article 

Journal of Virology, October 2001, p. 9096-9105, Vol. 75, No. 19
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.19.9096-9105.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Receptor Binding Transforms the Surface Subunit of the Mammalian C-Type Retrovirus Envelope Protein from an Inhibitor to an Activator of Fusion

Anna L. Barnett and James M. Cunningham*

Department of Medicine and Howard Hughes Medical Institute, Brigham and Women's Hospital, and Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts 02115

Received 16 April 2001/Accepted 26 June 2001

The envelope protein (Env) of murine leukemia viruses (MLVs) is composed of a surface subunit (SU) and a transmembrane subunit (TM), which mediates membrane fusion, resulting in infection. SU contains a discrete N-terminal receptor binding domain (RBD) that is connected to the remainder of Env by a short, proline-rich segment. Previous studies suggest that after receptor binding, the RBD interacts directly with the remainder of Env to trigger fusion (A. L. Barnett, R. A. Davey, and J. M. Cunningham, Proc. Natl. Acad. Sci. USA 98:4113-4118, 2001). To investigate the role of the RBD in activating fusion, we compared infection by several MLVs that are defective unless rescued in trans by the addition of soluble RBD to the culture medium. Infection by MLV lacking a critical histidine residue near the N terminus of the viral RBD is dependent on the expression of receptors for both the RBD in the viral Env and the soluble RBD supplied in trans. However, infection by MLVs in which the RBD has been deleted or replaced by the ligand erythropoietin are dependent only on expression of the receptor for the soluble RBD. We were able to expand the host range of xenotropic MLV to nonpermissive murine fibroblasts only if the RBD was deleted from the xenotropic viral envelope and the soluble RBD from ecotropic Friend MLV was supplied to the culture medium. These findings indicate that receptor binding transforms the RBD from an inhibitor to an activator of the viral fusion mechanism and that viruses lacking the critical histidine residue at the N terminus of the RBD are impaired at the activation step.

* Corresponding author. Mailing address: Room 1030, Thorn Building, Brigham and Women's Hospital, 75 Francis St., Boston, MA 02115. Phone: (617) 732-5852. Fax: (617) 738-5575. E-mail: cunningham{at}rascal.med.harvard.edu.

Journal of Virology, October 2001, p. 9096-9105, Vol. 75, No. 19
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.19.9096-9105.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Li, K., Zhang, S., Kronqvist, M., Wallin, M., Ekstrom, M., Derse, D., Garoff, H. (2008). Intersubunit Disulfide Isomerization Controls Membrane Fusion of Human T-Cell Leukemia Virus Env. J. Virol. 82: 7135-7143 [Abstract] [Full Text]  
  • Cheng, H. H., Anderson, M. M., Hankenson, F. C., Johnston, L., Kotwaliwale, C. V., Overbaugh, J. (2006). Envelope Determinants for Dual-Receptor Specificity in Feline Leukemia Virus Subgroup A and T Variants. J. Virol. 80: 1619-1628 [Abstract] [Full Text]  
  • Viejo-Borbolla, A., Thomas, P., Blair, E. D., Schulz, T. F. (2005). Increase in infectivity of targeted Moloney murine leukemia virus-based gene-delivery vectors through lowering the threshold for fusion. J. Gen. Virol. 86: 2469-2480 [Abstract] [Full Text]  
  • Farrell, K. B., Eiden, M. V. (2005). Dissection of Gammaretroviral Receptor Function by Using Type III Phosphate Transporters as Models. J. Virol. 79: 9332-9336 [Abstract] [Full Text]  
  • Burkhart, M. D., D'Agostino, P., Kayman, S. C., Pinter, A. (2005). Involvement of the C-Terminal Disulfide-Bonded Loop of Murine Leukemia Virus SU Protein in a Postbinding Step Critical for Viral Entry. J. Virol. 79: 7868-7876 [Abstract] [Full Text]  
  • Delos, S. E., Godby, J. A., White, J. M. (2005). Receptor-Induced Conformational Changes in the SU Subunit of the Avian Sarcoma/Leukosis Virus A Envelope Protein: Implications for Fusion Activation. J. Virol. 79: 3488-3499 [Abstract] [Full Text]  
  • Wallin, M., Ekstrom, M., Garoff, H. (2005). The Fusion-Controlling Disulfide Bond Isomerase in Retrovirus Env Is Triggered by Protein Destabilization. J. Virol. 79: 1678-1685 [Abstract] [Full Text]  
  • Vigdorovich, V., Strong, R. K., Miller, A. D. (2005). Expression and Characterization of a Soluble, Active Form of the Jaagsiekte Sheep Retrovirus Receptor, Hyal2. J. Virol. 79: 79-86 [Abstract] [Full Text]  
  • Cavaldesi, M., Caruso, M., Sthandier, O., Amati, P., Garcia, M. I. (2004). Conformational Changes of Murine Polyomavirus Capsid Proteins Induced by Sialic Acid Binding. J. Biol. Chem. 279: 41573-41579 [Abstract] [Full Text]  
  • Lavillette, D., Kabat, D. (2004). Porcine Endogenous Retroviruses Infect Cells Lacking Cognate Receptors by an Alternative Pathway: Implications for Retrovirus Evolution and Xenotransplantation. J. Virol. 78: 8868-8877 [Abstract] [Full Text]  
  • Lu, C.-W., Roth, M. J. (2003). Role of the Mutation Q252R in Activating Membrane Fusion in the Murine Leukemia Virus Surface Envelope Protein. J. Virol. 77: 10841-10849 [Abstract] [Full Text]  
  • Abrahamyan, L. G., Markosyan, R. M., Moore, J. P., Cohen, F. S., Melikyan, G. B. (2003). Human Immunodeficiency Virus Type 1 Env with an Intersubunit Disulfide Bond Engages Coreceptors but Requires Bond Reduction after Engagement To Induce Fusion. J. Virol. 77: 5829-5836 [Abstract] [Full Text]  
  • Wensel, D. L., Li, W., Cunningham, J. M. (2003). A Virus-Virus Interaction Circumvents the Virus Receptor Requirement for Infection by Pathogenic Retroviruses. J. Virol. 77: 3460-3469 [Abstract] [Full Text]  
  • Barnett, A. L., Wensel, D. L., Li, W., Fass, D., Cunningham, J. M. (2003). Structure and Mechanism of a Coreceptor for Infection by a Pathogenic Feline Retrovirus. J. Virol. 77: 2717-2729 [Abstract] [Full Text]  
  • Martin, F., Chowdhury, S., Neil, S. J., Chester, K. A., Cosset, F.-L., Collins, M. K. (2003). Targeted Retroviral Infection of Tumor Cells by Receptor Cooperation. J. Virol. 77: 2753-2756 [Abstract] [Full Text]  
  • Faix, P. H., Feldman, S. A., Overbaugh, J., Eiden, M. V. (2002). Host Range and Receptor Binding Properties of Vectors Bearing Feline Leukemia Virus Subgroup B Envelopes Can Be Modulated by Envelope Sequences outside of the Receptor Binding Domain. J. Virol. 76: 12369-12375 [Abstract] [Full Text]  
  • Lavillette, D., Ruggieri, A., Boson, B., Maurice, M., Cosset, F.-L. (2002). Relationship between SU Subdomains That Regulate the Receptor-Mediated Transition from the Native (Fusion-Inhibited) to the Fusion-Active Conformation of the Murine Leukemia Virus Glycoprotein. J. Virol. 76: 9673-9685 [Abstract] [Full Text]  
  • Gatot, J.-S., Callebaut, I., Van Lint, C., Demonte, D., Kerkhofs, P., Portetelle, D., Burny, A., Willems, L., Kettmann, R. (2002). Bovine Leukemia Virus SU Protein Interacts with Zinc, and Mutations within Two Interacting Regions Differently Affect Viral Fusion and Infectivity In Vivo. J. Virol. 76: 7956-7967 [Abstract] [Full Text]  
  • Lauring, A. S., Cheng, H. H., Eiden, M. V., Overbaugh, J. (2002). Genetic and Biochemical Analyses of Receptor and Cofactor Determinants for T-Cell-Tropic Feline Leukemia Virus Infection. J. Virol. 76: 8069-8078 [Abstract] [Full Text]  
  • Sandrin, V., Boson, B., Salmon, P., Gay, W., Negre, D., Le Grand, R., Trono, D., Cosset, F.-L. (2002). Lentiviral vectors pseudotyped with a modified RD114 envelope glycoprotein show increased stability in sera and augmented transduction of primary lymphocytes and CD34+ cells derived from human and nonhuman primates. Blood 100: 823-832 [Abstract] [Full Text]  
  • Farrell, K. B., Ting, Y.-T., Eiden, M. V. (2002). Fusion-Defective Gibbon Ape Leukemia Virus Vectors Can Be Rescued by Homologous but Not Heterologous Soluble Envelope Proteins. J. Virol. 76: 4267-4274 [Abstract] [Full Text]  


Copyright © 2010 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»