Yves Lepelletier,1,
Sophie Lambert,2,
Jean-Marie Fourneau,3
Vincent Blot,2
Sébastien Janvier,4
Bertrand Arnulf,1
Peter M. van Endert,3
Nikolaus Heveker,4
Claudine Pique,2,¶* and
Olivier Hermine1,¶*
CNRS UMR 8147, Université Paris V, Assistance Publique-Hôpitaux de Paris, Hôpital Necker, 161 rue de Sèvres, 75743 Paris Cedex 15, France,1 CNRS UMR 7151, Institut Universitaire d'Hématologie, Hôpital Saint Louis, 1 avenue Claude Vellefaux 75010, and Institut Cochin, CNRS UMR 8104-INSERM U567, Université René Descartes, Paris, France,2 INSERM U580, Hôpital Necker, 161 rue de Sèvres, 75743 Paris Cedex 15, France,3 Centre de Recherche 6737, Hôpital Sainte Justine, and Département de Biochimie, Université de Montréal, Montréal, Québec, Canada4
Received 27 December 2005/ Accepted 29 April 2006
Human T-cell lymphotropic virus type 1 (HTLV-1) is transmitted through a viral synapse and enters target cells via interaction with the glucose transporter GLUT1. Here, we show that Neuropilin-1 (NRP1), the receptor for semaphorin-3A and VEGF-A165 and a member of the immune synapse, is also a physical and functional partner of HTLV-1 envelope (Env) proteins. HTLV-1 Env and NRP1 complexes are formed in cotransfected cells, and endogenous NRP1 contributes to the binding of HTLV-1 Env to target cells. NRP1 overexpression increases HTLV-1 Env-dependent syncytium formation. Moreover, overexpression of NRP1 increases both HTLV-1 and HTLV-2 Env-dependent infection, whereas down-regulation of endogenous NRP1 has the opposite effect. Finally, overexpressed GLUT1, NRP1, and Env form ternary complexes in transfected cells, and endogenous NRP1 and GLUT1 colocalize in membrane junctions formed between uninfected and HTLV-1-infected T cells. These data show that NRP1 is involved in HTLV-1 and HTLV-2 entry, suggesting that the HTLV receptor has a multicomponent nature.
These authors contributed equally to this work.
¶ These authors contributed equally to this work.
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