Measles virus (MV) nucleoprotein binds to a novel cell surface receptor distinct from FcgammaRII via its C-terminal domain: role in MV-induced immunosuppression.
During acute measles virus (MV) infection, an efficient immune response occurs, followed by a transient but profound immunosuppression. MV nucleoprotein (MV-N) has been reported to induce both cellular and humoral immune responses and paradoxically to account for immunosuppression. Thus far, this latter activity has been attributed to MV-N binding to human and murine FcgammaRII. Here, we show that apoptosis of MV-infected human thymic epithelial cells (TEC) allows the release of MV-N in the extracellular compartment. This extracellular N is then able to bind either to MV-infected or uninfected TEC. We show that recombinant MV-N specifically binds to a membrane protein receptor, different from FcgammaRII, highly expressed on the cell surface of TEC. This new receptor is referred to as nucleoprotein receptor (NR). In addition, different Ns from other MV-related morbilliviruses can also bind to FcgammaRII and/or NR. We show that the region of MV-N responsible for binding to NR maps to the C-terminal fragment (N(TAIL)). Binding of MV-N to NR on TEC triggers sustained calcium influx and inhibits spontaneous cell proliferation by arresting cells in the G(0) and G(1) phases of the cell cycle. Finally, MV-N binds to both constitutively expressed NR on a large spectrum of cells from different species and to human activated T cells, leading to suppression of their proliferation. These results provide evidence that MV-N, after release in the extracellular compartment, binds to NR and thereby plays a role in MV-induced immunosuppression.
Laine
David
D
Laboratoire d'Immunobiologie Fondamentale et Clinique, INSERM U503, IFR128 BioSciences Lyon-Gerland, 69365 Lyon Cedex 07, France.
Trescol-Biémont
Marie-Claude
MC
Longhi
Sonia
S
Libeau
Geneviève
G
Marie
Julien C
JC
Vidalain
Pierre-Olivier
PO
Azocar
Olga
O
Diallo
Adama
A
Canard
Bruno
B
Rabourdin-Combe
Chantal
C
Valentin
Hélène
H
D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D004847:Epithelial Cells / Q000378:metabolism* / Q000821:virology; D006801:Humans; D007108:Immune Tolerance; D008213:Lymphocyte Activation; D008459:Measles virus / Q000378:metabolism / Q000472:pathogenicity*; D051379:Mice; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins / Q000235:genetics / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D017452:Receptors, IgG / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology*; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*
D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D011956:Receptors, Cell Surface; D017452:Receptors, IgG; D011994:Recombinant Proteins; D014764:Viral Proteins; C058314:nucleoprotein, Measles virus