Svoboda | Graniru | BBC Russia | Golosameriki | Facebook

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

Virology. 2007 Nov 25;368(2):351-62. doi: 10.1016/j.virol.2007.06.037. Epub 2007 Aug 7.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Humans
  • Interferon-alpha / metabolism
  • Interferon-beta / metabolism
  • Janus Kinase 1 / antagonists & inhibitors*
  • Janus Kinase 1 / metabolism
  • Phosphoproteins / metabolism*
  • Phosphorylation / drug effects
  • STAT1 Transcription Factor / antagonists & inhibitors
  • STAT1 Transcription Factor / metabolism
  • Signal Transduction
  • Transfection
  • Two-Hybrid System Techniques
  • Viral Proteins / metabolism*

Substances

  • Interferon-alpha
  • Phosphoproteins
  • STAT1 Transcription Factor
  • STAT1 protein, human
  • V protein, measles virus
  • Viral Proteins
  • Interferon-beta
  • Janus Kinase 1