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Updated: May 23, 2025

Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production
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Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production

Published on: March 2, 2014

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Mpox virus poxin-schlafen fusion protein suppresses innate antiviral response by sequestering STAT2

Pearl Chan1, Zi-Wei Ye1, Wenlong Zhao1

  • 1School of Biomedical Sciences, The University of Hong Kong, Pokfulam, Hong Kong.

Emerging Microbes & Infections
|March 11, 2025
PubMed

Insights

Mpox virus Poxin-schlafen (PoxS) protein hinders host antiviral defenses by sequestering STAT2, blocking interferon-stimulated gene expression and promoting viral replication. This reveals a key mechanism of viral immune evasion.

Area of Science:

  • Virology
  • Immunology
  • Molecular Biology

Background:

  • Mpox virus (MPXV) requires effective interferon (IFN) antagonism for replication.
  • The specific MPXV-encoded IFN antagonists remain largely uncharacterized.

Purpose of the Study:

  • To characterize the IFN antagonism of the MPXV poxin-schlafen (PoxS) fusion gene.
  • To elucidate the mechanism by which MPXV PoxS interferes with host antiviral responses.

Main Methods:

  • Investigated the enzymatic activity of MPXV PoxS on 2'3'-cGAMP.
  • Assessed the impact of MPXV PoxS on cGAS-STING signaling and type I IFN production.
  • Analyzed the effect of MPXV PoxS on the expression of IFN-stimulated genes (ISGs).
  • Determined the interaction of MPXV PoxS with host factors, including STAT2, using co-immunoprecipitation.

Main Results:

  • MPXV PoxS reduces 2'3'-cGAMP levels but does not inhibit cGAS-STING-mediated type I IFN production.
  • MPXV PoxS antagonizes basal and type I IFN-induced ISG expression by inhibiting interferon-stimulated response elements.
  • MPXV PoxS interacts with STAT2, sequestering it in the cytoplasm, which is crucial for suppressing ISG expression.
  • Both the schlafen fusion and nuclease activity of PoxS are necessary for STAT2 sequestration and ISG suppression.

Conclusions:

  • MPXV PoxS antagonizes host antiviral immunity by sequestering STAT2, thereby preventing the expression of antiviral genes.
  • This mechanism allows MPXV to evade type I IFN-mediated suppression of viral replication.
Keywords:
2′3′-cGAMP hydrolaseSTAT2STINGcGASinnate antiviral responsemonkeypox virusmpox viruspoxin

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