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Poxvirus A51R proteins regulate microtubule stability and antagonize a cell-intrinsic antiviral response

Dahee Seo1, Sabrynna Brito Oliveira2, Emily A Rex1

  • 1Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

Cell Reports
|March 8, 2024
PubMed

Insights

Vaccinia virus (VV) protein A51R stabilizes host microtubules, preventing a reactive oxygen species (ROS) antiviral response. This microtubule interaction is crucial for poxvirus virulence and replication in animals.

Area of Science:

  • Virology
  • Cell Biology
  • Structural Biology

Background:

  • Viruses frequently manipulate host cell structures, including microtubule (MT) networks, but the mechanisms and purposes are often unknown.
  • The vaccinia virus (VV) A51R protein's role in host cell interactions requires elucidation.

Purpose of the Study:

  • To investigate the function of the vaccinia virus (VV) A51R protein in modulating host cell microtubules.
  • To determine the role of A51R-microtubule interactions in viral pathogenesis and host antiviral responses.

Main Methods:

  • Biochemical assays to characterize A51R as a microtubule-associated protein (MAP).
  • Analysis of conserved residues mediating A51R-MT interactions.
  • Infection studies using wild-type and mutant viruses to assess antiviral response suppression and virulence in a mouse model.

Main Results:

  • VV A51R protein directly binds and stabilizes microtubules by promoting growth and inhibiting depolymerization.
  • Conserved, positively charged residues in A51R mediate these microtubule interactions.
  • Viruses with MT interaction-deficient A51R fail to suppress a reactive oxygen species (ROS)-dependent antiviral response in macrophages, blocking virion morphogenesis.
  • A51R-MT interactions are essential for VV virulence in mice.

Conclusions:

  • Poxviral A51R protein functions as a MAP, stabilizing host microtubules.
  • These MAP-MT interactions are critical for overcoming a macrophage cell-intrinsic ROS antiviral response, enabling virus morphogenesis and replication.
  • A51R-MT interactions are a key determinant of VV virulence.
Keywords:
CP: Cell biologyCP: Microbiologycytoskeletonimmune evasionpoxvirusreactive oxygen speciesviral pathogenesisvirus-host interactions

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