Measles virus V protein blocks Jak1-mediated phosphorylation of STAT1 to escape IFN-alpha/beta signaling.
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.
Laboratoire de Génomique Virale et Vaccination, CNRS URA 3015, Institut Pasteur, 28 rue du Dr. Roux, 75724 Paris Cedex 15, France.
Grégory
G
Caignard
Mathilde
M
Guerbois
Jean-Louis
JL
Labernardière
Yves
Y
Jacob
Louis M
LM
Jones
Fabian
F
Wild
Frédéric
F
Tangy
Pierre-Olivier
PO
Vidalain
D002460:Cell Line; D006801:Humans; D016898:Interferon-alpha / Q000378:metabolism; D016899:Interferon-beta / Q000378:metabolism; D053613:Janus Kinase 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D050794:STAT1 Transcription Factor / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection; D020798:Two-Hybrid System Techniques; D014764:Viral Proteins / Q000378:metabolism*
D016898:Interferon-alpha; D010750:Phosphoproteins; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; C069181:V protein, measles virus; D014764:Viral Proteins; D016899:Interferon-beta; D053613:Janus Kinase 1