ArticleJournal of virology2000
Sequential CD4-coreceptor interactions in human immunodeficiency virus type 1 Env function: soluble CD4 activates Env for coreceptor-dependent fusion and reveals blocking activities of antibodies against cryptic conserved epitopes on gp120.
Article in Journal of virology, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 132 citations in OpenAlex.
- Roles of lncRNAs in the transcription regulation of HIV-1.Biomedical journal · 2022Review
- Article
- Antiviral Activity of HIV gp120-Targeting Bispecific T Cell Engager Antibody Constructs.Journal of virology · 2018Article
- HIV-1 inhibitory properties of eCD4-Igmim2 determined using an Env-mediated membrane fusion assay.PloS one · 2018Article
- Control of HIV Infection In Vivo Using Gene Therapy with a Secreted Entry Inhibitor.Molecular therapy. Nucleic acids · 2017Article
- Cross-Linking of a CD4-Mimetic Miniprotein with HIV-1 Env gp140 Alters Kinetics and Specificities of Antibody Responses against HIV-1 Env in Macaques.Journal of virology · 2017Article
- Plasticity and Epitope Exposure of the HIV-1 Envelope Trimer.Journal of virology · 2017Article
- Cryo-EM structure of a CD4-bound open HIV-1 envelope trimer reveals structural rearrangements of the gp120 V1V2 loop.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Article
- The emerging role of long non-coding RNAs in HIV infection.Virus research · 2016Review
- Antigenic properties of the human immunodeficiency virus envelope glycoprotein gp120 on virions bound to target cells.PLoS pathogens · 2015Article
- Antibody potency relates to the ability to recognize the closed, pre-fusion form of HIV Env.Nature communications · 2015Article
- Distinct mechanisms regulate exposure of neutralizing epitopes in the V2 and V3 loops of HIV-1 envelope.Journal of virology · 2014Article
- A novel gene therapy strategy using secreted multifunctional anti-HIV proteins to confer protection to gene-modified and unmodified target cells.Gene therapy · 2014Article
- Defining differential genetic signatures in CXCR4- and the CCR5-utilizing HIV-1 co-linear sequences.PloS one · 2014Article
- Computer-Aided Approaches for Targeting HIVgp41.Biology · 2012Article
- Acquisition of CD4-dependence by CD4-independent SIV passaged in human peripheral blood mononuclear cells.Retrovirology · 2012Article
- Intraprotomer masking of third variable loop (V3) epitopes by the first and second variable loops (V1V2) within the native HIV-1 envelope glycoprotein trimer.Proceedings of the National Academy of Sciences of the United States of America · 2011Article
- Conformational and structural features of HIV-1 gp120 underlying the dual receptor antagonism by cross-reactive neutralizing antibody m18.Biochemistry · 2011Article
- Cloning, expression and purification of Microcystis viridis lectin in Escherichia coli.Molecular biotechnology · 2011Article
2 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
We devised an experimental system to examine sequential events by which the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) interacts with CD4 and coreceptor to induce membrane fusion. Recombinant soluble CD4 (sCD4) activated fusion between effector cells expressing Env and target cells expressing coreceptor (CCR5 or CXCR4) but lacking CD4. sCD4-activated fusion was dose dependent, occurred comparably with two- and four-domain proteins, and demonstrated Env-coreceptor specificities parallel to those reported in conventional fusion and infectivity systems. Fusion activation occurred upon sCD4 preincubation and washing of the Env-expressing effector cells but not the coreceptor-bearing target cells, thereby demonstrating that sCD4 exerts its effects by acting on Env. These findings provide direct functional evidence for a sequential two-step model of Env-receptor interactions, whereby gp120 binds first to CD4 and becomes activated for subsequent functional interaction with coreceptor, leading to membrane fusion. We used the sCD4-activated system to explore neutralization by the anti-gp120 human monoclonal antibodies 17b and 48d. These antibodies reportedly bind conserved CD4-induced epitopes involved in coreceptor interactions but neutralize HIV-1 infection only weakly. We found that 17b and 48d had minimal effects in the standard cell fusion system using target cells expressing both CD4 and coreceptor but potently blocked sCD4-activated fusion with target cells expressing coreceptor alone. Both antibodies strongly inhibited sCD4-activated fusion by Envs from genetically diverse HIV-1 isolates. Thus, the sCD4-activated system reveals conserved Env-blocking epitopes that are masked in native Env and hence not readily detected by conventional systems.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.