HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 276, Issue 32, 30335-30341, August 10, 2001

This Article Full Text Full Text (PDF) All Versions of this Article: 276/32/30335    most recent M103788200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Dimitrov, A. S. Articles by Blumenthal, R. Search for Related Content PubMed PubMed Citation Articles by Dimitrov, A. S. Articles by Blumenthal, R. Social Bookmarking                      What's this?

Early Intermediates in HIV-1 Envelope Glycoprotein-mediated Fusion Triggered by CD4 and Co-receptor Complexes^*

Antony S. Dimitrov, Xiaodong Xiao, Dimiter S. Dimitrov, and Robert Blumenthal

From the Laboratory of Experimental and Computational Biology, Center for Cancer Research, NCI, National Institutes of Health, Frederick, Maryland 21702

An early step in the process of HIV-1 entry into target cells is the activation of its envelope glycoprotein (GP120-GP41) to a fusogenic state upon binding to target cell CD4 and cognate co-receptor. Incubation of human immunodeficiency virus (HIV)-1 Env-expressing cells with an excess of CD4 and co-recepeptor-bearing target cells resulted in an influx of an impermeant nucleic acid-staining fluorescent dye into the Env-expressing cells. The dye influx occurred concomitant with cell fusion. No influx of dye into target cells was observed if they were incubated with an excess of Env-expressing cells. The permeabilization of Env-expressing cells was also triggered by CD4·co-receptor complexes attached to Protein G-Sepharose beads in the absence of target cells. The CD4 and co-receptor-induced permeabilization of Env-expressing cells occurred with the same specificity with respect to co-receptor usage as cell fusion. Natural ligands for the co-receptors and C-terminal GP41 peptide inhibitors of HIV-1 fusion blocked this effect. Our results indicate that the process of HIV-1 Env-mediated fusion is initiated by the destabilization of HIV-1 Env-expressing membranes. Further elucidation of these early intermediates may help identify and develop potential inhibitors of HIV-1 entry into cells.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				J. J. Chang, F. Wightman, A. Bartholomeusz, A. Ayres, S. J. Kent, J. Sasadeusz, and S. R. Lewin Reduced Hepatitis B Virus (HBV)-Specific CD4+ T-Cell Responses in Human Immunodeficiency Virus Type 1-HBV-Coinfected Individuals Receiving HBV-Active Antiretroviral Therapy J. Virol., March 1, 2005; 79(5): 3038 - 3051. [Abstract] [Full Text] [PDF]

				J. Daecke, O. T. Fackler, M. T. Dittmar, and H.-G. Krausslich Involvement of Clathrin-Mediated Endocytosis in Human Immunodeficiency Virus Type 1 Entry J. Virol., February 1, 2005; 79(3): 1581 - 1594. [Abstract] [Full Text] [PDF]

				T. Koshiba and D. C. Chan The Prefusogenic Intermediate of HIV-1 gp41 Contains Exposed C-peptide Regions J. Biol. Chem., February 21, 2003; 278(9): 7573 - 7579. [Abstract] [Full Text] [PDF]

				A. Saez-Cirion, S. Nir, M. Lorizate, A. Agirre, A. Cruz, J. Perez-Gil, and J. L. Nieva Sphingomyelin and Cholesterol Promote HIV-1 gp41 Pretransmembrane Sequence Surface Aggregation and Membrane Restructuring J. Biol. Chem., June 7, 2002; 277(24): 21776 - 21785. [Abstract] [Full Text] [PDF]

				M. Moulard, S. K. Phogat, Y. Shu, A. F. Labrijn, X. Xiao, J. M. Binley, M.-Y. Zhang, I. A. Sidorov, C. C. Broder, J. Robinson, et al. Broadly cross-reactive HIV-1-neutralizing human monoclonal Fab selected for binding to gp120-CD4-CCR5 complexes PNAS, May 14, 2002; 99(10): 6913 - 6918. [Abstract] [Full Text] [PDF]