The anti-HIV pentameric pseudopeptide HB-19 binds the C-terminal end of nucleolin and prevents anchorage of virus particles in the plasma membrane of target cells

Sébastien Nisole, Elias A. Said, Claudia Mische, Marie Christine Prevost, Bernard Krust, Philippe Bouvet, Alberto Bianco, Jean Paul Briandand, Ara G. Hovanessian

Research output: Contribution to journalArticle

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Abstract

The multivalent pseudopeptide HB-19 that binds the cell-surface-expressed nucleolin is a potent inhibitor of human immunodeficiency virus (HIV) infection by blocking virus particle attachment and thus anchorage in the plasma membrane. We show that cross-linking of surface-bound HB-19A (like HB-19 but with a modified template) results in aggregation of HB-19A with surface nucleolin. Consistent with its specific action, HB-19A binding to different types of cells reaches saturation at concentrations that have been reported to result in inhibition of HIV infection. By using Chinese hamster ovary mutant cell lines, we confirm that the binding of HB-19A to surface nucleolin is independent of heparan and chondroitin sulfate proteoglycans. In vitro generated full-length nucleolin was found to bind HB-19A, whereas the N-terminal part containing the acidic amino acid stretches of nucleolin did not. The use of various deletion constructs of the C-terminal part of nucleolin then permitted the identification of the extreme C-terminal end of nucleolin, containing repeats of the amino acid motif, RGG, as the domain that binds HB-19A. Finally, a synthetic peptide corresponding to the last C-terminal 63 amino acids was able to inhibit HIV infection at the stage of HIV attachment to cells, thus suggesting that this domain could be functional in the HIV anchorage process.

Original languageEnglish
Pages (from-to)20877-20886
Number of pages10
JournalJournal of Biological Chemistry
Volume277
Issue number23
DOIs
Publication statusPublished - Jun 7 2002

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Cell membranes
Viruses
Virion
Cell Membrane
HIV
Virus Diseases
Virus Attachment
Acidic Amino Acids
Chondroitin Sulfate Proteoglycans
Amino Acids
Heparan Sulfate Proteoglycans
Amino Acid Motifs
Cricetulus
nucleolin
Ovary
Agglomeration
Cells
Cell Line
Peptides

ASJC Scopus subject areas

  • Biochemistry

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The anti-HIV pentameric pseudopeptide HB-19 binds the C-terminal end of nucleolin and prevents anchorage of virus particles in the plasma membrane of target cells. / Nisole, Sébastien; Said, Elias A.; Mische, Claudia; Prevost, Marie Christine; Krust, Bernard; Bouvet, Philippe; Bianco, Alberto; Briandand, Jean Paul; Hovanessian, Ara G.

In: Journal of Biological Chemistry, Vol. 277, No. 23, 07.06.2002, p. 20877-20886.

Research output: Contribution to journalArticle

Nisole, Sébastien ; Said, Elias A. ; Mische, Claudia ; Prevost, Marie Christine ; Krust, Bernard ; Bouvet, Philippe ; Bianco, Alberto ; Briandand, Jean Paul ; Hovanessian, Ara G. / The anti-HIV pentameric pseudopeptide HB-19 binds the C-terminal end of nucleolin and prevents anchorage of virus particles in the plasma membrane of target cells. In: Journal of Biological Chemistry. 2002 ; Vol. 277, No. 23. pp. 20877-20886.
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