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HTLV-1 uses HSPG and neuropilin-1 for entry by molecular mimicry of VEGF165.

ABSTRACT: 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 VEGF(165), are essential for HTLV-1 entry. Here we investigated whether, as when binding VEGF(165), HSPGs and NRP-1 work in concert during HTLV-1 entry. VEGF(165) binds to the b domain of NRP-1 through both HSPG-dependent and -independent interactions, the latter involving its exon 8. We show that VEGF(165) is a selective competitor of HTLV-1 entry and that HTLV-1 mimics VEGF(165) 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 VEGF(165); (3) the formation of Env/NRP-1 complexes is enhanced by HSPGs; and (4) the HTLV SU contains a motif homologous to VEGF(165) 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.

SUBMITTER: Lambert S

PROVIDER: S-EPMC2686187 | biostudies-literature | 2009 May

REPOSITORIES: biostudies-literature

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HTLV-1 uses HSPG and neuropilin-1 for entry by molecular mimicry of VEGF165.

Lambert Sophie S Bouttier Manuella M Vassy Roger R Seigneuret Michel M Petrow-Sadowski Cari C Janvier Sébastien S Heveker Nikolaus N Ruscetti Francis W FW Perret Gérard G Jones Kathryn S KS Pique Claudine C

Blood 20090306 21

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 VEGF(165), are essential for HTLV-1 entry. Here we investigated whether, as when binding VEGF(165), HSPGs and NRP-1 work in concert during HTLV-1 entry. VEGF(165) binds to the b domain of NRP-1 through both HSPG-depen ...[more]

PMID: 19270265

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Dataset Information

HTLV-1 uses HSPG and neuropilin-1 for entry by molecular mimicry of VEGF165.

Publications

HTLV-1 uses HSPG and neuropilin-1 for entry by molecular mimicry of VEGF165.

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