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Updated: Aug 8, 2026

Imaging of HIV-1 Envelope-induced Virological Synapse and Signaling on Synthetic Lipid Bilayers
Published on: March 8, 2012
Early intermediates in HIV-1 envelope glycoprotein-mediated fusion triggered by CD4 and co-receptor complexes
A S Dimitrov1, X Xiao, D S Dimitrov
1Laboratory of Experimental and Computational Biology, Center for Cancer Research, NCI, National Institutes of Health, Frederick, Maryland 21702, USA.
Insights
HIV-1 entry involves envelope glycoprotein (GP120-GP41) activation. This process destabilizes HIV-1 Env-expressing cell membranes, initiating fusion and offering targets for new entry inhibitors.
Area of Science:
- Virology
- Cell Biology
- Biochemistry
Background:
- Human immunodeficiency virus type 1 (HIV-1) entry into target cells is a complex process initiated by the envelope glycoprotein (GP120-GP41).
- GP120-GP41 must transition to a fusogenic state upon binding to target cell CD4 and a co-receptor to facilitate viral entry.
Purpose of the Study:
- To investigate the early membrane events during HIV-1 envelope-mediated fusion.
- To identify potential targets for novel HIV-1 entry inhibitors.
Main Methods:
- Incubation of HIV-1 Env-expressing cells with target cells or CD4.co-receptor complexes on beads.
- Monitoring dye influx into Env-expressing cells as an indicator of membrane permeabilization.
- Assessing the effect of co-receptor ligands and GP41 peptide inhibitors on permeabilization.
Main Results:
- HIV-1 Env-expressing cells showed dye influx and permeabilization upon incubation with CD4 and co-receptor-bearing target cells, correlating with cell fusion.
- Permeabilization was also induced by CD4.co-receptor complexes on beads, independent of target cells.
- This permeabilization exhibited co-receptor specificity and was blocked by natural co-receptor ligands and GP41 peptide inhibitors.
Conclusions:
- HIV-1 envelope-mediated fusion is initiated by the destabilization of the viral envelope-expressing cell membrane.
- Understanding these early membrane intermediates is crucial for developing inhibitors of HIV-1 entry.
Abstract:
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.
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