Poxvirus A51R proteins regulate microtubule stability and antagonize a cell-intrinsic antiviral response
Dahee Seo,
Sabrynna Brito Oliveira,
Emily A. Rex,
Xuecheng Ye,
Luke M. Rice,
Flávio Guimarães da Fonseca,
Don B. Gammon
Affiliations
Dahee Seo
Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
Sabrynna Brito Oliveira
Laboratório de Virologia Básica e Aplicada, Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG 31270-901, Brazil
Emily A. Rex
Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
Xuecheng Ye
Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
Luke M. Rice
Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
Flávio Guimarães da Fonseca
Laboratório de Virologia Básica e Aplicada, Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG 31270-901, Brazil
Don B. Gammon
Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Corresponding author
Summary: 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.
