Cell surface–associated Tat modulates HIV-1 infection and spreading through a specific interaction with gp120 viral envelope protein

Human immunodeficiency virus-1 (HIV-1) Tat, a nuclear transactivator of viral gene expression, has the unusual property of being released by infected cells. Recent studies suggest that extracellular Tat is partially sequestered by heparan sulfate proteoglycans. As a consequence, Tat is concentrated...

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Bibliographic Details
Published in:Blood 2005-04, Vol.105 (7), p.2802-2811
Main Authors: Marchiò, Serena, Alfano, Massimo, Primo, Luca, Gramaglia, Daniela, Butini, Luca, Gennero, Luisa, De Vivo, Enrico, Arap, Wadih, Giacca, Mauro, Pasqualini, Renata, Bussolino, Federico
Format: Article
Language:English
Subjects:
Biological and medical sciences
Gene Products, tat - metabolism
HIV Envelope Protein gp120 - chemistry
HIV Envelope Protein gp120 - metabolism
HIV Infections - metabolism
HIV-1 - metabolism
HIV-1 - pathogenicity
Human viral diseases
Humans
In Vitro Techniques
Infectious diseases
Ligands
Medical sciences
Membrane Proteins - metabolism
Molecular Mimicry
Neutrophils - metabolism
Neutrophils - virology
Peptide Library
Protein Binding
tat Gene Products, Human Immunodeficiency Virus
U937 Cells
Viral diseases
Viral diseases of the lymphoid tissue and the blood. Aids
Virulence
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Summary:Human immunodeficiency virus-1 (HIV-1) Tat, a nuclear transactivator of viral gene expression, has the unusual property of being released by infected cells. Recent studies suggest that extracellular Tat is partially sequestered by heparan sulfate proteoglycans. As a consequence, Tat is concentrated on the cell surface and protected from proteolytic degradation, thus remaining in a biologically active form. We show that Tat binds the surfaces of both HIV-1–infected and surrounding uninfected cells. We provide evidence for a specific interaction between Tat and the HIV-1 glycoprotein 120 (gp120) envelope protein, which enhances virus attachment and entry into cells. We map the interacting sites of both Tat and gp120 and show that synthetic peptides mimicking the gp120 site inhibit HIV-1 infection. Our data demonstrate that membrane-associated Tat is a novel modulator of virus entry and suggest that the Tat-gp120 interaction represents a critical step in HIV-1 spreading during the course of infection.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood-2004-06-2212