Inhibition of IFN-alpha/beta signaling by two discrete peptides within measles virus V protein that specifically bind STAT1 and STAT2

Virology. 2009 Jan 5;383(1):112-20. doi: 10.1016/j.virol.2008.10.014. Epub 2008 Nov 12.


The V protein of measles virus (MV-V) is a potent inhibitor of IFN-alpha/beta signaling pathway. We previously reported that when physically dissociated, the N-terminal and C-terminal regions of MV-V (PNT and VCT, respectively) could independently impair signal transduction. The PNT region inhibited IFN-alpha/beta signaling by interacting with at least two components of this pathway: Jak1 and STAT1. Here we report a direct interaction between the VCT of MV-V and STAT2, a third component of IFN-alpha/beta transduction machinery. This interaction with STAT2 is carried by the cysteine-constrained peptide of 49 amino acids localized in the VCT region, and is essential to the inhibition of IFN-alpha/beta signaling. In parallel, we also mapped STAT1 binding site in the PNT region and identified a minimal peptide of only 11 amino acids. IFN-alpha/beta signaling was impaired in human cells treated with this MV-V peptide fused to a cell-penetrating sequence. Finally, we show that signaling downstream of IFN-lambda, a recently identified cytokine that also relies on STAT1, STAT2 and Jak1 to transduce, is blocked by MV-V. Altogether, our results illustrate how a single viral protein has evolved to achieve a robust inhibition of the antiviral response by interacting with several signaling molecules.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Cell Line
  • Humans
  • Interferon-alpha / antagonists & inhibitors*
  • Interferon-beta / antagonists & inhibitors*
  • Measles virus / immunology*
  • Models, Molecular
  • Molecular Sequence Data
  • Phosphoproteins / metabolism*
  • Protein Binding
  • Protein Interaction Mapping
  • Protein Structure, Tertiary
  • STAT1 Transcription Factor / metabolism*
  • STAT2 Transcription Factor / metabolism*
  • Sequence Alignment
  • Viral Proteins / metabolism*


  • Interferon-alpha
  • Phosphoproteins
  • STAT1 Transcription Factor
  • STAT1 protein, human
  • STAT2 Transcription Factor
  • STAT2 protein, human
  • V protein, measles virus
  • Viral Proteins
  • Interferon-beta