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PMID: 7693970 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't

Conformational changes induced in the envelope glycoproteins of the human and simian immunodeficiency viruses by soluble receptor binding.

Journal of virology ·Vol. 67 ·No. 12 ·1993-12-00 ·Pages 7383-93

Sattentau QJ, Moore JP, Vignaux F, Traincard F, Poignard P

Abstract

We have investigated the molecular basis of biological differences observed among cell line-adapted isolates of the human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2) and the simian immunodeficiency virus (SIV) in response to receptor binding by using a soluble form of CD4 (sCD4) as a receptor mimic. We find that sCD4 binds to the envelope glycoproteins of all of the HIV-1 isolates tested with affinities within a threefold range, whereas those of the HIV-2 and SIV isolates have relative affinities for sCD4 two- to eightfold lower than those of HIV-1. Treatment of infected cells with sCD4 induced the dissociation of gp120 from gp41 and increased the exposure of a cryptic gp41 epitope on all of the HIV-1 isolates. By contrast, neither dissociation of the outer envelope glycoprotein nor increased exposure of the transmembrane glycoprotein was observed when sCD4 bound to HIV-2- or SIV-infected cells. Moreover, immunoprecipitation with sCD4 resulted in the coprecipitation of the surface and transmembrane glycoproteins from virions of the HIV-2 and SIV isolates, whereas the surface envelope glycoprotein alone was precipitated from HIV-1. However, treatment of HIV-1-, HIV-2-, and SIV-infected cells with sCD4 did result in an increase in exposure of their V2 and V3 loops, as detected by enhanced antibody reactivity. This demonstrates that receptor binding to the outer envelope glycoprotein induces certain conformational changes which are common to all of these viruses and others which are restricted to cell line-passaged isolates of HIV-1.

MeSH Terms
CD4 Antigens/metabolism,pharmacology Cell Fusion/drug effects Cells, Cultured Dose-Response Relationship, Drug Epitopes Gene Products, env/metabolism HIV/metabolism HIV Antibodies/metabolism HIV Antigens/metabolism HIV Envelope Protein gp120/metabolism HIV Envelope Protein gp41/metabolism HIV-1/metabolism HIV-2/metabolism Humans Protein Conformation Receptors, HIV/metabolism Receptors, Virus/metabolism Simian Immunodeficiency Virus/metabolism Viral Envelope Proteins/metabolism env Gene Products, Human Immunodeficiency Virus
Chemicals
CD4 Antigens Epitopes Gene Products, env HIV Antibodies HIV Antigens HIV Envelope Protein gp120 HIV Envelope Protein gp41 Receptors, HIV Receptors, Virus Viral Envelope Proteins env Gene Products, Human Immunodeficiency Virus env protein gp36, Human immunodeficiency virus
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Sattentau Q J
Centre d'Immunologie de Marseille-Luminy, Marseille, France.
Moore J P
Vignaux F
Traincard F
Poignard P
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.67.12.7383-7393.1993
Published
1993-12-00
Pages
7383-93
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC238202
Subset
IM
External Links
PubMed source DOI: 10.1128/JVI.67.12.7383-7393.1993 PMC Full Text View journal details
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