Measles virus V protein blocks Jak1-mediated phosphorylation of STAT1 to escape IFN-{alpha}/{beta} signaling
- Laboratoire de Genomique Virale et Vaccination, CNRS URA 3015, Institut Pasteur, 28 rue du Dr. Roux, 75724 Paris Cedex 15 (France)
- Unite Postulante de Genetique, Papillomavirus et Cancer Humain, 25 rue du Dr. Roux, 75724 Paris Cedex 15 (France)
- Groupe Logiciels et Banques de Donnees, Institut Pasteur, 28 rue du Dr. Roux, 75724 Paris Cedex 15 (France)
- INSERM U404-Immunity and Vaccination, IFR128-BioSciences, 21 Avenue Tony Garnier, Lyon-Gerland, 69365 Lyon Cedex 07 (France)
Viruses have evolved various strategies to escape the antiviral activity of type I interferons (IFN-{alpha}/{beta}). For measles virus, this function is carried by the polycistronic gene P that encodes, by an unusual editing strategy, for the phosphoprotein P and the virulence factor V (MV-V). MV-V prevents STAT1 nuclear translocation by either sequestration or phosphorylation inhibition, thereby blocking IFN-{alpha}/{beta} pathway. We show that both the N- and C-terminal domains of MV-V (PNT and VCT) contribute to the inhibition of IFN-{alpha}/{beta} signaling. Using the two-hybrid system and co-affinity purification experiments, we identified STAT1 and Jak1 as interactors of MV-V and demonstrate that MV-V can block the direct phosphorylation of STAT1 by Jak1. A deleterious mutation within the PNT domain of MV-V (Y110H) impaired its ability to interact and block STAT1 phosphorylation. Thus, MV-V interacts with at least two components of IFN-{alpha}/{beta} receptor complex to block downstream signaling.
- OSTI ID:
- 21077996
- Journal Information:
- Virology, Vol. 368, Issue 2; Other Information: DOI: 10.1016/j.virol.2007.06.037; PII: S0042-6822(07)00467-9; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0042-6822
- Country of Publication:
- United States
- Language:
- English
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