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

Abstract : 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.
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https://hal-pasteur.archives-ouvertes.fr/pasteur-00360178
Contributor : Mireille Gau <>
Submitted on : Tuesday, February 10, 2009 - 3:27:09 PM
Last modification on : Monday, January 13, 2020 - 5:08:10 PM

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Grégory Caignard, Mehdi Bouraï, Yves Jacob, The Infection-Mapping Project I-Map, Frédéric Tangy, et al.. Inhibition of IFN-alpha/beta signaling by two discrete peptides within measles virus V protein that specifically bind STAT1 and STAT2.. Virology, Elsevier, 2009, 383 (1), pp.112-20. ⟨10.1016/j.virol.2008.10.014⟩. ⟨pasteur-00360178⟩

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