Neuropilin-1 is involved in human T-cell lymphotropic virus type 1 entry.
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.
Ghez
David
D
CNRS UMR 8147, Université Paris V, Assistance Publique-Hôpitaux de Paris, Hôpital Necker, 161 rue de Sèvres, 75743 Paris Cedex 15, France.
Lepelletier
Yves
Y
Lambert
Sophie
S
Fourneau
Jean-Marie
JM
Blot
Vincent
V
Janvier
Sébastien
S
Arnulf
Bertrand
B
van Endert
Peter M
PM
Heveker
Nikolaus
N
Pique
Claudine
C
Hermine
Olivier
O
D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D015536:Down-Regulation / Q000235:genetics; D015686:Gene Products, env / Q000235:genetics / Q000378:metabolism*; D015726:Giant Cells / Q000378:metabolism / Q000821:virology; D051272:Glucose Transporter Type 1 / Q000235:genetics / Q000378:metabolism*; D015490:HTLV-I Infections / Q000235:genetics / Q000378:metabolism* / Q000635:transmission; D015491:HTLV-II Infections / Q000235:genetics / Q000378:metabolism / Q000635:transmission; D006367:HeLa Cells; D015368:Human T-lymphotropic virus 1 / Q000235:genetics / Q000378:metabolism*; D015367:Human T-lymphotropic virus 2 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism; D039942:Neuropilin-1 / Q000235:genetics / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism*; D040121:Semaphorin-3A / Q000378:metabolism; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D015686:Gene Products, env; D051272:Glucose Transporter Type 1; D046912:Multiprotein Complexes; D010446:Peptide Fragments; D011991:Receptors, Virus; C108639:SEMA3A protein, human; D040121:Semaphorin-3A; D042461:Vascular Endothelial Growth Factor A; C511613:vascular endothelial growth factor A (138-165); D039942:Neuropilin-1