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 Lineberger, J. E.
Right arrow Articles by Miller, M. D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lineberger, J. E.
Right arrow Articles by Miller, M. D.

 Previous Article  |  Next Article 

Journal of Virology, April 2002, p. 3522-3533, Vol. 76, No. 7
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.7.3522-3533.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Altering Expression Levels of Human Immunodeficiency Virus Type 1 gp120-gp41 Affects Efficiency but Not Kinetics of Cell-Cell Fusion

Janet E. Lineberger, Renee Danzeisen, Daria J. Hazuda, Adam J. Simon, and Michael D. Miller*

Department of Biological Chemistry, Merck Research Laboratories, West Point, Pennsylvania 19486

Received 2 August 2001/ Accepted 4 January 2002

Human immunodeficiency virus (HIV) entry into a host cell requires the fusion of virus and cellular membranes that is driven by interaction of the viral envelope glycoproteins gp120 and gp41 (gp120/gp41) with CD4 and a coreceptor, typically either CXCR4 or CCR5. The stoichiometry of gp120/gp41:CD4:CCR5 necessary to initiate membrane fusion is not known. To allow an examination of early events in gp120/gp41-driven membrane fusion, we developed a novel real-time cell-cell fusion assay. Using this assay to study fusion kinetics, we found that altering the cell surface density of gp120/gp41 affected the maximal extent of fusion without dramatically altering fusion kinetics. Collectively, these observations are consistent with the view that gp120/gp41-driven membrane fusion requires the formation of a threshold number of fusion-active intercellular gp120/gp41:CD4:CCR5 complexes. Furthermore, the probability of reaching this threshold is governed, in part, by the surface density of gp120/gp41.

* Corresponding author. Mailing address: Department of Biological Chemistry, Merck Research Laboratories, P.O. Box 4, WP16-101, West Point, PA 19486. Phone: (215) 652-0480. Fax: (215) 652-0994. E-mail: michael_miller1{at}merck.com.

Journal of Virology, April 2002, p. 3522-3533, Vol. 76, No. 7
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.7.3522-3533.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Ray, N., Blackburn, L. A., Doms, R. W. (2009). HR-2 Mutations in Human Immunodeficiency Virus Type 1 gp41 Restore Fusion Kinetics Delayed by HR-1 Mutations That Cause Clinical Resistance to Enfuvirtide. J. Virol. 83: 2989-2995 [Abstract] [Full Text]  
  • Pastore, C., Nedellec, R., Ramos, A., Hartley, O., Miamidian, J. L., Reeves, J. D., Mosier, D. E. (2007). Conserved Changes in Envelope Function during Human Immunodeficiency Virus Type 1 Coreceptor Switching. J. Virol. 81: 8165-8179 [Abstract] [Full Text]  
  • Aguilar, H. C., Matreyek, K. A., Choi, D. Y., Filone, C. M., Young, S., Lee, B. (2007). Polybasic KKR Motif in the Cytoplasmic Tail of Nipah Virus Fusion Protein Modulates Membrane Fusion by Inside-Out Signaling. J. Virol. 81: 4520-4532 [Abstract] [Full Text]  
  • Chan, E., Heilek-Snyder, G., Cammack, N., Sankuratri, S., Ji, C. (2006). Development of a Moloney Murine Leukemia Virus-Based Pseudotype Anti-HIV Assay Suitable for Accurate and Rapid Evaluation of HIV Entry Inhibitors. J Biomol Screen 11: 652-663 [Abstract]  
  • Aguilar, H. C., Matreyek, K. A., Filone, C. M., Hashimi, S. T., Levroney, E. L., Negrete, O. A., Bertolotti-Ciarlet, A., Choi, D. Y., McHardy, I., Fulcher, J. A., Su, S. V., Wolf, M. C., Kohatsu, L., Baum, L. G., Lee, B. (2006). N-Glycans on Nipah Virus Fusion Protein Protect against Neutralization but Reduce Membrane Fusion and Viral Entry.. J. Virol. 80: 4878-4889 [Abstract] [Full Text]  
  • Ji, C., Zhang, J., Cammack, N., Sankuratri, S. (2006). Development of a Novel Dual CCR5-Dependent and CXCR4-Dependent Cell-Cell Fusion Assay System with Inducible gp160 Expression. J Biomol Screen 11: 65-74 [Abstract]  
  • Bianchi, E., Finotto, M., Ingallinella, P., Hrin, R., Carella, A. V., Hou, X. S., Schleif, W. A., Miller, M. D., Geleziunas, R., Pessi, A. (2005). Covalent stabilization of coiled coils of the HIV gp41 N region yields extremely potent and broad inhibitors of viral infection. Proc. Natl. Acad. Sci. USA 102: 12903-12908 [Abstract] [Full Text]  
  • Mkrtchyan, S. R., Markosyan, R. M., Eadon, M. T., Moore, J. P., Melikyan, G. B., Cohen, F. S. (2005). Ternary Complex Formation of Human Immunodeficiency Virus Type 1 Env, CD4, and Chemokine Receptor Captured as an Intermediate of Membrane Fusion. J. Virol. 79: 11161-11169 [Abstract] [Full Text]  
  • Marozsan, A. J., Moore, D. M., Lobritz, M. A., Fraundorf, E., Abraha, A., Reeves, J. D., Arts, E. J. (2005). Differences in the Fitness of Two Diverse Wild-Type Human Immunodeficiency Virus Type 1 Isolates Are Related to the Efficiency of Cell Binding and Entry. J. Virol. 79: 7121-7134 [Abstract] [Full Text]  
  • Reeves, J. D., Lee, F.-H., Miamidian, J. L., Jabara, C. B., Juntilla, M. M., Doms, R. W. (2005). Enfuvirtide Resistance Mutations: Impact on Human Immunodeficiency Virus Envelope Function, Entry Inhibitor Sensitivity, and Virus Neutralization. J. Virol. 79: 4991-4999 [Abstract] [Full Text]  
  • Abrahamyan, L. G., Mkrtchyan, S. R., Binley, J., Lu, M., Melikyan, G. B., Cohen, F. S. (2005). The Cytoplasmic Tail Slows the Folding of Human Immunodeficiency Virus Type 1 Env from a Late Prebundle Configuration into the Six-Helix Bundle. J. Virol. 79: 106-115 [Abstract] [Full Text]  
  • Potgens, A.J.G., Drewlo, S., Kokozidou, M., Kaufmann, P. (2004). Syncytin: the major regulator of trophoblast fusion? Recent developments and hypotheses on its action. Hum Reprod Update 10: 487-496 [Abstract] [Full Text]  
  • Reeves, J. D., Miamidian, J. L., Biscone, M. J., Lee, F.-H., Ahmad, N., Pierson, T. C., Doms, R. W. (2004). Impact of Mutations in the Coreceptor Binding Site on Human Immunodeficiency Virus Type 1 Fusion, Infection, and Entry Inhibitor Sensitivity. J. Virol. 78: 5476-5485 [Abstract] [Full Text]  
  • Simmons, G., Rennekamp, A. J., Chai, N., Vandenberghe, L. H., Riley, J. L., Bates, P. (2003). Folate Receptor Alpha and Caveolae Are Not Required for Ebola Virus Glycoprotein-Mediated Viral Infection. J. Virol. 77: 13433-13438 [Abstract] [Full Text]  
  • O'Reilly, L., Roth, M. J. (2003). G541R within the 4070A TM Protein Regulates Fusion in Murine Leukemia Viruses. J. Virol. 77: 12011-12021 [Abstract] [Full Text]  
  • Poumbourios, P., Maerz, A. L., Drummer, H. E. (2003). Functional Evolution of the HIV-1 Envelope Glycoprotein 120 Association Site of Glycoprotein 41. J. Biol. Chem. 278: 42149-42160 [Abstract] [Full Text]  
  • Tobiume, M., Lineberger, J. E., Lundquist, C. A., Miller, M. D., Aiken, C. (2003). Nef Does Not Affect the Efficiency of Human Immunodeficiency Virus Type 1 Fusion with Target Cells. J. Virol. 77: 10645-10650 [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]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»