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

Serena Marchiò, Massimo Alfano, Luca Primo, Daniela Gramaglia, Luca Butini, Luisa Gennero, Enrico De Vivo, Wadih Arap, Mauro Giacca, Renata Pasqualini, Federico Bussolino

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2802-2811
Number of pages10
JournalBlood
Volume105
Issue number7
DOIs
Publication statusPublished - Apr 1 2005

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Viral Envelope Proteins
Virus Diseases
Viruses
HIV-1
Glycoproteins
Virus Internalization
Virus Attachment
Heparan Sulfate Proteoglycans
Trans-Activators
Viral Genes
Gene expression
Modulators
Gene Expression
Peptides
Membranes
Infection
Degradation
Proteins

ASJC Scopus subject areas

  • Hematology

Cite this

Cell surface-associated Tat modulates HIV-1 infection and spreading through a specific interaction with gp120 viral envelope protein. / Marchiò, Serena; Alfano, Massimo; Primo, Luca; Gramaglia, Daniela; Butini, Luca; Gennero, Luisa; De Vivo, Enrico; Arap, Wadih; Giacca, Mauro; Pasqualini, Renata; Bussolino, Federico.

In: Blood, Vol. 105, No. 7, 01.04.2005, p. 2802-2811.

Research output: Contribution to journalArticle

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AU - Butini, Luca

AU - Gennero, Luisa

AU - De Vivo, Enrico

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