Work

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

Year: 2001

Type: article

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.

Source: Journal of Biological Chemistry

DOI: 10.1074/jbc.m103788200

Authors: Antony S. Dimitrov, Xiaodong Xiao, Dimiter S. Dimitrov, Robert Blumenthal

Institutions: National Institutes of Health, Frederick National Laboratory for Cancer Research, National Cancer Institute, Center for Cancer Research

Language: English

Topic: HIV Research and Treatment

Subfield: Virology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $3,430