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Journal of Virology, November 2004, p. 11952-11961, Vol. 78, No. 21
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.21.11952-11961.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Cell Surface Delivery of the Measles Virus Nucleoprotein: a Viral Strategy To Induce Immunosuppression{dagger}

Julien C. Marie,1,{ddagger} Frédéric Saltel,2,{ddagger} Jean-Michel Escola,3 Pierre Jurdic,2 T. Fabian Wild,1 and Branka Horvat1*

INSERM U404,1 UMR 5665, INRA 913, ENS-Lyon, IFR 128, Lyon, France,2 Department of Dermatology, University Hospital of Geneva, Geneva, Switzerland3

Received 25 March 2004/ Accepted 14 July 2004

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 Fc{gamma} receptor. Nucleoprotein is then expressed at the surfaces of infected leukocytes associated with the Fc{gamma} 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.

* Corresponding author. Mailing address: INSERM U404, 21 Avenue Tony Garnier, 69365 Lyon, France. Phone: 33 4 37 28 24 56. Fax: 33 4 37 28 23 91. E-mail: horvat{at}cervi-lyon.inserm.fr.

{dagger} Supplemental material for this article may be found at http://jvi.asm.org/.

{ddagger} J.C.M. and F.S contributed equally to this work.

Journal of Virology, November 2004, p. 11952-11961, Vol. 78, No. 21
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.21.11952-11961.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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