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Type I Interferon: Monkeypox/Mpox Viruses Achilles Heel?

Jacqueline Williams1,2,3, James Bonner1,2,3,4, Karen Kibler1,2,3

  • 1Biodesign Center for Immunotherapy, Vaccines and Virotherapy, Arizona State University, Tempe, USA.

Advances in Experimental Medicine and Biology
|May 27, 2024
PubMed
Summary
This summary is machine-generated.

Monkeypox virus (MPXV) is sensitive to interferon treatment because it cannot fully block Z- Как это перевести на русский язык?BP1-dependent antiviral pathways. This inability to inhibit necroptotic cell death is a key vulnerability for MPXV.

Keywords:
InterferonMonkeypox/mpox virusOrthopoxvirusesRIPK3 (receptor-interacting protein kinase 3)Z-DNAZ-RNAZBP1 (Z-DNA-binding protein 1)

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Area of Science:

  • Virology
  • Immunology
  • Cell Biology

Background:

  • Poxviruses possess numerous genes to evade host innate immunity.
  • Chordopoxviruses encode at least three inhibitors of necroptotic cell death: E3, vIRD, and vMLKL.
  • The necroptotic pathway is crucial for inhibiting chordopoxvirus replication.

Purpose of the Study:

  • To investigate the implications of lost necroptotic inhibitors in chordopoxviruses.
  • To understand the unique interferon sensitivity of Monkeypox virus (MPXV).

Main Methods:

  • Comparative analysis of poxvirus E3 homologues.
  • Examination of Z-BP1 activation and necroptosis inhibition.
  • Assessment of MPXV sensitivity to interferon (IFN) treatment.

Main Results:

  • MPXV has a truncated E3 homologue, lacking the N-terminal domain.
  • This truncation impairs the inhibition of interferon-inducible Z-BP1.
  • MPXV exhibits sensitivity to IFN treatment in mammals with complete necroptotic pathways.

Conclusions:

  • The inability to fully inhibit Z-BP1-dependent antiviral pathways is a significant vulnerability for MPXV.
  • Interferon sensitivity represents an Achilles' heel for poxviruses like MPXV that cannot fully suppress innate antiviral mechanisms.
  • Understanding these viral evasion strategies is critical for developing effective antiviral therapies.