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.
Original language | English (US) |
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Article number | 113882 |
Journal | Cell Reports |
Volume | 43 |
Issue number | 3 |
DOIs | |
State | Published - Mar 26 2024 |
Keywords
- CP: Cell biology
- CP: Microbiology
- cytoskeleton
- immune evasion
- poxvirus
- reactive oxygen species
- viral pathogenesis
- virus-host interactions
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology