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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 (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 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 Citing Articles via Google Scholar Google Scholar Articles by Lambert, S. Articles by Pique, C. Search for Related Content PubMed PubMed Citation Articles by Lambert, S. Articles by Pique, C. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted April 11, 2008 Accepted February 27, 2009 HTLV-1 uses HSPG and neuropilin 1 for entry by molecular mimicry of VEGF165 Sophie Lambert, Manuella Bouttier, Roger Vassy, Michel Seigneuret, Cari Petrow-Sadowski, Sebastien Janvier, Nikolaus Heveker, Francis W. Ruscetti, Gerard Perret, Kathryn S. Jones, and Claudine Pique* CNRS UMR 8104, INSERM U567, Universite Paris-Descartes, Institut Cochin, Paris, France Universite Paris 13, UMR 7033, Bobigny, France Basic Science Program, SAIC-Frederick, Inc., National Cancer Institute-Frederick, Frederick, MD, United States Centre de Recherche 6737, Hopital Sainte Justine and Departement de Biochimie, Universite de Montreal, Montreal, QC, Canada Laboratory of Experimental Immunology, Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute-Frederick, Frederick, MD, United States * Corresponding author; email: claudine.pique{at}inserm.fr. HTLV-1 entry involves the interaction between the surface (SU) subunit of the Env proteins and cellular receptor(s). Previously, our laboratories independently 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 HSPG-independent interactions; the latter involving its exon 8-encoded domain. We show that VEGF165 is a selective competitor of HTLV-1 entry and that HTLV-1 mimics VEGF165 to recruit HSPGs and NRP-1: i) the NRP-1 b domain is required for HTLV-1 binding, ii) SU binding to target cells is blocked by the HSPG-binding domain of VEGF165; iii) the formation of Env/NRP-1 complexes is enhanced by HSPGs and iv) the HTLV SU contains a conserved motif homologous to VEGF165 exon 8. This SU 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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