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Blood, 21 May 2009, Vol. 113, No. 21, pp. 5176-5185. Prepublished online as a Blood First Edition Paper on March 6, 2009; DOI 10.1182/blood-2008-04-150342. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2008-04-150342v1 113/21/5176    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Google Scholar Articles by Lambert, S. Articles by Pique, C. PubMed PubMed Citation Articles by Lambert, S. Articles by Pique, C. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY HTLV-1 uses HSPG and neuropilin-1 for entry by molecular mimicry of VEGF165 Sophie Lambert1,*, Manuella Bouttier1,*, Roger Vassy2, Michel Seigneuret1, Cari Petrow-Sadowski3, Sébastien Janvier4, Nikolaus Heveker4, Francis W. Ruscetti5, Gérard Perret2, Kathryn S. Jones3,, and Claudine Pique1, 1 Centre National de la Recherche Scientifique Unite Mixte de Recherche 8104, Inserm U567, Université Paris-Descartes, Institut Cochin, Paris, France; 2 Université Paris 13, Unite Mixte de Recherche 7033, Bobigny, France; 3 Basic Science Program, Science Applications International Corporation-Frederick, National Cancer Institute, Frederick, MD; 4 Centre de Recherche 6737, Hôpital Sainte Justine and Département de Biochimie, Université de Montréal, Montréal, QC; and 5 Laboratory of Experimental Immunology, Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, Frederick, MD Human T-cell lymphotropic virus type 1 (HTLV-1) entry involves the interaction between the surface (SU) subunit of the Env proteins and cellular receptor(s). Previously, our laboratories demonstrated that heparan sulfate proteoglycans (HSPGs) and neuropilin-1 (NRP-1), a receptor of VEGF165, are essential for HTLV-1 entry. Here we investigated whether, as when binding VEGF165, HSPGs and NRP-1 work in concert during HTLV-1 entry. VEGF165 binds to the b domain of NRP-1 through both HSPG-dependent and -independent interactions, the latter involving its exon 8. We show that VEGF165 is a selective competitor of HTLV-1 entry and that HTLV-1 mimics VEGF165 to recruit HSPGs and NRP-1: (1) the NRP-1 b domain is required for HTLV-1 binding; (2) SU binding to target cells is blocked by the HSPG-binding domain of VEGF165; (3) the formation of Env/NRP-1 complexes is enhanced by HSPGs; and (4) the HTLV SU contains a motif homologous to VEGF165 exon 8. This motif directly binds to NRP-1 and is essential for HTLV-1 binding to, internalization into, and infection of CD4+ T cells and dendritic cells. These findings demonstrate that HSPGs and NRP-1 function as HTLV-1 receptors in a cooperative manner and reveal an unexpected mimicry mechanism that may have major implications in vivo. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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