HTLV-1 uses HSPG and neuropilin-1 for entry by molecular mimicry of VEGF165
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- Sophie Lambert
- Centre National de la Recherche Scientifique Unite Mixte de Recherche 8104, Inserm U567, Université Paris-Descartes, Institut Cochin, Paris, France;
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- Manuella Bouttier
- Centre National de la Recherche Scientifique Unite Mixte de Recherche 8104, Inserm U567, Université Paris-Descartes, Institut Cochin, Paris, France;
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- Roger Vassy
- Université Paris 13, Unite Mixte de Recherche 7033, Bobigny, France;
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- Michel Seigneuret
- Centre National de la Recherche Scientifique Unite Mixte de Recherche 8104, Inserm U567, Université Paris-Descartes, Institut Cochin, Paris, France;
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- Cari Petrow-Sadowski
- Basic Science Program, Science Applications International Corporation-Frederick, National Cancer Institute, Frederick, MD;
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- Sébastien Janvier
- Centre de Recherche 6737, Hôpital Sainte Justine and Département de Biochimie, Université de Montréal, Montréal, QC; and
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- Nikolaus Heveker
- Centre de Recherche 6737, Hôpital Sainte Justine and Département de Biochimie, Université de Montréal, Montréal, QC; and
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- Francis W. Ruscetti
- Laboratory of Experimental Immunology, Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, Frederick, MD
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- Gérard Perret
- Université Paris 13, Unite Mixte de Recherche 7033, Bobigny, France;
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- Kathryn S. Jones
- Basic Science Program, Science Applications International Corporation-Frederick, National Cancer Institute, Frederick, MD;
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- Claudine Pique
- Centre National de la Recherche Scientifique Unite Mixte de Recherche 8104, Inserm U567, Université Paris-Descartes, Institut Cochin, Paris, France;
Description
<jats:title>Abstract</jats:title><jats:p>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.</jats:p>
Journal
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- Blood
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Blood 113 (21), 5176-5185, 2009-05-21
American Society of Hematology
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Details 詳細情報について
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- CRID
- 1363951795849084800
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- ISSN
- 15280020
- 00064971
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- Data Source
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- Crossref