Measles virus V protein blocks Jak1-mediated phosphorylation of STAT1 to escape IFN-{alpha}/{beta} signaling

Journal Article · Sun Nov 25 00:00:00 EST 2007 · Virology

DOI:https://doi.org/10.1016/j.virol.2007.06.037· OSTI ID:21077996

Caignard, Gregory; Guerbois, Mathilde; Labernardiere, Jean-Louis ^[1]; Jacob, Yves ^[2]; Jones, Louis M ^[3]; Wild, Fabian ^[4]; Tangy, Frederic ^[1]; Vidalain, Pierre-Olivier ^[1]

---

1. Laboratoire de Genomique Virale et Vaccination, CNRS URA 3015, Institut Pasteur, 28 rue du Dr. Roux, 75724 Paris Cedex 15 (France)
2. Unite Postulante de Genetique, Papillomavirus et Cancer Humain, 25 rue du Dr. Roux, 75724 Paris Cedex 15 (France)
3. Groupe Logiciels et Banques de Donnees, Institut Pasteur, 28 rue du Dr. Roux, 75724 Paris Cedex 15 (France)
4. 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

Related Subjects

60 APPLIED LIFE SCIENCES
GENES
HYBRID SYSTEMS
INHIBITION
INTERFERON
MEASLES VIRUS
MUTATIONS
PHOSPHOPROTEINS
PHOSPHORYLATION
PURIFICATION
RECEPTORS
TRANSLOCATION
VIRULENCE