Cell surface delivery of the measles virus nucleoprotein: a viral strategy to induce immunosuppression.
Although only a few blood cells are infected during measles, this infectious disease is followed by acute immunosuppression, associated with high infant mortality. Measles virus nucleoprotein has been suggested to contribute to virus-induced inhibition of the immune response. However, it has been difficult to understand how this cytosolic viral protein could leave an infected cell and then perturb the immune response. Here we demonstrate that intracellularly synthesized nucleoprotein enters the late endocytic compartment, where it recruits its cellular ligand, the Fcgamma receptor. Nucleoprotein is then expressed at the surfaces of infected leukocytes associated with the Fcgamma receptor and is secreted into the extracellular compartment, allowing its interaction with uninfected cells. Finally, cell-derived nucleoprotein inhibits the secretion of interleukin-12 and the generation of the inflammatory reaction, both shown to be impaired during measles. These results reveal nucleoprotein egress from infected cells as a novel strategy in measles-induced immunosuppression.
INSERM U404, 21 Avenue Tony Garnier, 69365 Lyon, France.
Julien C
JC
Marie
Frédéric
F
Saltel
Jean-Michel
JM
Escola
Pierre
P
Jurdic
T Fabian
TF
Wild
Branka
B
Horvat
D002462:Cell Membrane / Q000378:metabolism; D003877:Dermatitis, Contact / Q000209:etiology; D004705:Endocytosis; D006801:Humans; D007108:Immune Tolerance; D018664:Interleukin-12 / Q000378:metabolism; D053762:Interleukin-12 Subunit p40; D008459:Measles virus / Q000502:physiology*; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins / Q000378:metabolism*; D021122:Protein Subunits / Q000378:metabolism; D017452:Receptors, IgG / Q000502:physiology; D014764:Viral Proteins / Q000378:metabolism*
D053762:Interleukin-12 Subunit p40; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D021122:Protein Subunits; D017452:Receptors, IgG; D014764:Viral Proteins; C058314:nucleoprotein, Measles virus; D018664:Interleukin-12