Pleiotrophin inhibits HIV infection by binding the cell surface-expressed nucleolin

Elias A. Said, José Courty, Josette Svab, Jean Delbé, Bernard Krust, Ara G. Hovanessian

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

The growth factor pleiotrophin (PTN) has been reported to bind heparan sulfate and nucleolin, two components of the cell surface implicated in the attachment of HIV-1 particles to cells. Here we show that PTN inhibits HIV-1 infection by its capacity to inhibit HIV-1 particle attachment to the surface of permissive cells. The β-sheet domains of PTN appear to be implicated in this inhibitory effect on the HIV infection, in particular the domain containing amino acids 60-110. PTN binding to the cell surface is mediated by high and low affinity binding sites. Other inhibitors of HIV attachment known to bind specifically surface expressed nucleolin, such as the pseudopeptide HB-19 and the cytokine midkine prevent the binding of PTN to its low affinity-binding site. Confocal immunofluorescence laser microscopy revealed that the cross-linking of surface-bound PTN with a specific antibody results in the clustering of cell surface-expressed nucleolin and the colocalization of both PTN and nucleolin signals. Following its binding to surface-nucleolin, PTN is internalized by a temperature sensitive mechanism, a process which is inhibited by HB-19 and is independent of heparan and chondroitin sulfate proteoglycans. Nevertheless, proteoglycans might play a role in the concentration of PTN on the cell surface for a more efficient interaction with nucleolin. Our results demonstrate for the first time that PTN inhibits HIV infection and suggest that the cell surface-expressed nucleolin is a low affinity receptor for PTN binding to cells and it is also implicated in PTN entry into cells by an active process.

Original languageEnglish
Pages (from-to)4646-4659
Number of pages14
JournalFEBS Journal
Volume272
Issue number18
DOIs
Publication statusPublished - Sep 2005

Fingerprint

HIV Infections
HIV-1
Confocal Microscopy
pleiotrophin
nucleolin
Binding Sites
Chondroitin Sulfate Proteoglycans
Heparan Sulfate Proteoglycans
Heparitin Sulfate
Proteoglycans
Cellular Structures
Fluorescence Microscopy
Cluster Analysis
Intercellular Signaling Peptides and Proteins
Microscopic examination
HIV
Cytokines
Amino Acids
Temperature
Antibodies

Keywords

  • Binding
  • HIV
  • Pleiotrophin
  • Receptor
  • Surface nucleolin

ASJC Scopus subject areas

  • Biochemistry

Cite this

Pleiotrophin inhibits HIV infection by binding the cell surface-expressed nucleolin. / Said, Elias A.; Courty, José; Svab, Josette; Delbé, Jean; Krust, Bernard; Hovanessian, Ara G.

In: FEBS Journal, Vol. 272, No. 18, 09.2005, p. 4646-4659.

Research output: Contribution to journalArticle

Said, EA, Courty, J, Svab, J, Delbé, J, Krust, B & Hovanessian, AG 2005, 'Pleiotrophin inhibits HIV infection by binding the cell surface-expressed nucleolin', FEBS Journal, vol. 272, no. 18, pp. 4646-4659. https://doi.org/10.1111/j.1742-4658.2005.04870.x
Said, Elias A. ; Courty, José ; Svab, Josette ; Delbé, Jean ; Krust, Bernard ; Hovanessian, Ara G. / Pleiotrophin inhibits HIV infection by binding the cell surface-expressed nucleolin. In: FEBS Journal. 2005 ; Vol. 272, No. 18. pp. 4646-4659.
@article{9f8dc8a7805d4c2f8f7c990a417e18de,
title = "Pleiotrophin inhibits HIV infection by binding the cell surface-expressed nucleolin",
abstract = "The growth factor pleiotrophin (PTN) has been reported to bind heparan sulfate and nucleolin, two components of the cell surface implicated in the attachment of HIV-1 particles to cells. Here we show that PTN inhibits HIV-1 infection by its capacity to inhibit HIV-1 particle attachment to the surface of permissive cells. The β-sheet domains of PTN appear to be implicated in this inhibitory effect on the HIV infection, in particular the domain containing amino acids 60-110. PTN binding to the cell surface is mediated by high and low affinity binding sites. Other inhibitors of HIV attachment known to bind specifically surface expressed nucleolin, such as the pseudopeptide HB-19 and the cytokine midkine prevent the binding of PTN to its low affinity-binding site. Confocal immunofluorescence laser microscopy revealed that the cross-linking of surface-bound PTN with a specific antibody results in the clustering of cell surface-expressed nucleolin and the colocalization of both PTN and nucleolin signals. Following its binding to surface-nucleolin, PTN is internalized by a temperature sensitive mechanism, a process which is inhibited by HB-19 and is independent of heparan and chondroitin sulfate proteoglycans. Nevertheless, proteoglycans might play a role in the concentration of PTN on the cell surface for a more efficient interaction with nucleolin. Our results demonstrate for the first time that PTN inhibits HIV infection and suggest that the cell surface-expressed nucleolin is a low affinity receptor for PTN binding to cells and it is also implicated in PTN entry into cells by an active process.",
keywords = "Binding, HIV, Pleiotrophin, Receptor, Surface nucleolin",
author = "Said, {Elias A.} and Jos{\'e} Courty and Josette Svab and Jean Delb{\'e} and Bernard Krust and Hovanessian, {Ara G.}",
year = "2005",
month = "9",
doi = "10.1111/j.1742-4658.2005.04870.x",
language = "English",
volume = "272",
pages = "4646--4659",
journal = "FEBS Journal",
issn = "1742-464X",
publisher = "Wiley-Blackwell",
number = "18",

}

TY - JOUR

T1 - Pleiotrophin inhibits HIV infection by binding the cell surface-expressed nucleolin

AU - Said, Elias A.

AU - Courty, José

AU - Svab, Josette

AU - Delbé, Jean

AU - Krust, Bernard

AU - Hovanessian, Ara G.

PY - 2005/9

Y1 - 2005/9

N2 - The growth factor pleiotrophin (PTN) has been reported to bind heparan sulfate and nucleolin, two components of the cell surface implicated in the attachment of HIV-1 particles to cells. Here we show that PTN inhibits HIV-1 infection by its capacity to inhibit HIV-1 particle attachment to the surface of permissive cells. The β-sheet domains of PTN appear to be implicated in this inhibitory effect on the HIV infection, in particular the domain containing amino acids 60-110. PTN binding to the cell surface is mediated by high and low affinity binding sites. Other inhibitors of HIV attachment known to bind specifically surface expressed nucleolin, such as the pseudopeptide HB-19 and the cytokine midkine prevent the binding of PTN to its low affinity-binding site. Confocal immunofluorescence laser microscopy revealed that the cross-linking of surface-bound PTN with a specific antibody results in the clustering of cell surface-expressed nucleolin and the colocalization of both PTN and nucleolin signals. Following its binding to surface-nucleolin, PTN is internalized by a temperature sensitive mechanism, a process which is inhibited by HB-19 and is independent of heparan and chondroitin sulfate proteoglycans. Nevertheless, proteoglycans might play a role in the concentration of PTN on the cell surface for a more efficient interaction with nucleolin. Our results demonstrate for the first time that PTN inhibits HIV infection and suggest that the cell surface-expressed nucleolin is a low affinity receptor for PTN binding to cells and it is also implicated in PTN entry into cells by an active process.

AB - The growth factor pleiotrophin (PTN) has been reported to bind heparan sulfate and nucleolin, two components of the cell surface implicated in the attachment of HIV-1 particles to cells. Here we show that PTN inhibits HIV-1 infection by its capacity to inhibit HIV-1 particle attachment to the surface of permissive cells. The β-sheet domains of PTN appear to be implicated in this inhibitory effect on the HIV infection, in particular the domain containing amino acids 60-110. PTN binding to the cell surface is mediated by high and low affinity binding sites. Other inhibitors of HIV attachment known to bind specifically surface expressed nucleolin, such as the pseudopeptide HB-19 and the cytokine midkine prevent the binding of PTN to its low affinity-binding site. Confocal immunofluorescence laser microscopy revealed that the cross-linking of surface-bound PTN with a specific antibody results in the clustering of cell surface-expressed nucleolin and the colocalization of both PTN and nucleolin signals. Following its binding to surface-nucleolin, PTN is internalized by a temperature sensitive mechanism, a process which is inhibited by HB-19 and is independent of heparan and chondroitin sulfate proteoglycans. Nevertheless, proteoglycans might play a role in the concentration of PTN on the cell surface for a more efficient interaction with nucleolin. Our results demonstrate for the first time that PTN inhibits HIV infection and suggest that the cell surface-expressed nucleolin is a low affinity receptor for PTN binding to cells and it is also implicated in PTN entry into cells by an active process.

KW - Binding

KW - HIV

KW - Pleiotrophin

KW - Receptor

KW - Surface nucleolin

UR - http://www.scopus.com/inward/record.url?scp=25444530635&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=25444530635&partnerID=8YFLogxK

U2 - 10.1111/j.1742-4658.2005.04870.x

DO - 10.1111/j.1742-4658.2005.04870.x

M3 - Article

VL - 272

SP - 4646

EP - 4659

JO - FEBS Journal

JF - FEBS Journal

SN - 1742-464X

IS - 18

ER -