Ghez David, Lepelletier Yves, Lambert Sophie, Fourneau Jean-Marie, Blot Vincent, Janvier Sébastien, Arnulf Bertrand, van Endert Peter M, Heveker Nikolaus, Pique Claudine, Hermine Olivier
CNRS UMR 8147, Université Paris V, Assistance Publique-Hôpitaux de Paris, Hôpital Necker, 161 rue de Sèvres, 75743 Paris Cedex 15, France.
J Virol. 2006 Jul;80(14):6844-54. doi: 10.1128/JVI.02719-05.
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.
人类嗜T细胞病毒1型（HTLV-1）通过病毒突触进行传播，并通过与葡萄糖转运蛋白GLUT1相互作用进入靶细胞。在此，我们发现神经纤毛蛋白-1（NRP1），即信号素-3A和血管内皮生长因子-A165的受体以及免疫突触的一个成员，也是HTLV-1包膜（Env）蛋白的一个物理和功能伙伴。HTLV-1 Env与NRP1复合物在共转染细胞中形成，内源性NRP1有助于HTLV-1 Env与靶细胞的结合。NRP1的过表达增加了HTLV-1 Env依赖的合胞体形成。此外，NRP1的过表达增加了HTLV-1和HTLV-2 Env依赖的感染，而内源性NRP1的下调则产生相反的效果。最后，过表达的GLUT1、NRP1和Env在转染细胞中形成三元复合物，并且内源性NRP1和GLUT1在未感染和HTLV-1感染的T细胞之间形成的膜连接处共定位。这些数据表明NRP1参与了HTLV-1和HTLV-2的进入，提示HTLV受体具有多组分性质。
