1. Poxvirus A51R proteins regulate microtubule stability and antagonize a cell-intrinsic antiviral response.
- Author
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Seo D, Brito Oliveira S, Rex EA, Ye X, Rice LM, da Fonseca FG, and Gammon DB
- Subjects
- Animals, Mice, Reactive Oxygen Species metabolism, Vaccinia virus physiology, Viral Proteins metabolism, Microtubules metabolism, Antiviral Agents metabolism, Virus Replication, Poxviridae genetics
- Abstract
Numerous viruses alter host microtubule (MT) networks during infection, but how and why they induce these changes is unclear in many cases. We show that the vaccinia virus (VV)-encoded A51R protein is a MT-associated protein (MAP) that directly binds MTs and stabilizes them by both promoting their growth and preventing their depolymerization. Furthermore, we demonstrate that A51R-MT interactions are conserved across A51R proteins from multiple poxvirus genera, and highly conserved, positively charged residues in A51R proteins mediate these interactions. Strikingly, we find that viruses encoding MT interaction-deficient A51R proteins fail to suppress a reactive oxygen species (ROS)-dependent antiviral response in macrophages that leads to a block in virion morphogenesis. Moreover, A51R-MT interactions are required for VV virulence in mice. Collectively, our data show that poxviral MAP-MT interactions overcome a cell-intrinsic antiviral ROS response in macrophages that would otherwise block virus morphogenesis and replication in animals., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
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