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Title: The West Nile virus assembly process evades the conserved antiviral mechanism of the interferon-induced MxA protein

Flaviviruses have evolved means to evade host innate immune responses. Recent evidence suggests this is due to prevention of interferon production and signaling in flavivirus-infected cells. Here we show that the interferon-induced MxA protein can sequester the West Nile virus strain Kunjin virus (WNV{sub KUN}) capsid protein in cytoplasmic tubular structures in an expression-replication system. This sequestering resulted in reduced titers of secreted WNV{sub KUN} particles. We show by electron microscopy, tomography and 3D modeling that these cytoplasmic tubular structures form organized bundles. Additionally we show that recombinant ER-targeted MxA can restrict production of infectious WNV{sub KUN} under conditions of virus infection. Our results indicate a co-ordinated and compartmentalized WNV{sub KUN} assembly process may prevent recognition of viral components by MxA, particularly the capsid protein. This recognition can be exploited if MxA is targeted to intracellular sites of WNV{sub KUN} assembly. This results in further understanding of the mechanisms of flavivirus evasion from the immune system. - Highlights: • We show that the ISG MxA can recognize the West Nile virus capsid protein. • Interaction between WNV C protein and MxA induces cytoplasmic fibrils. • MxA can be retargeted to the ER to restrict WNV particle release. • WNV assemblymore » process is a strategy to avoid MxA recognition.« less
Authors:
 [1] ;  [2] ;  [3] ; ;  [4] ;  [1] ;  [3] ;  [2] ;  [3]
  1. School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane (Australia)
  2. Department of Microbiology, La Trobe University, Melbourne (Australia)
  3. (Australia)
  4. Institute for Molecular Bioscience, University of Queensland, Brisbane (Australia)
Publication Date:
OSTI Identifier:
22435001
Resource Type:
Journal Article
Resource Relation:
Journal Name: Virology; Journal Volume: 448; Other Information: Copyright (c) 2013 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ELECTRON MICROSCOPY; IMMUNITY; INTERFERON; PARTICLES; SIMULATION; TOMOGRAPHY; VIRUSES