Recognition by host nuclear transport proteins drives disorder-to-order transition in Hendra virus v

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13 Citations (Scopus)

Abstract

Hendra virus (HeV) is a paramyxovirus that causes lethal disease in humans, for which no vaccine or antiviral agent is available. HeV V protein is central to pathogenesis through its ability to interact with cytoplasmic host proteins, playing key antiviral roles. Here we use immunoprecipitation, siRNA knockdown and confocal laser scanning microscopy to show that HeV V shuttles to and from the nucleus through specific host nuclear transporters. Spectroscopic and small angle X-ray scattering studies reveal HeV V undergoes a disorder-to-order transition upon binding to either importin α/β1 or exportin-1/Ran-GTP, dependent on the V N-terminus. Importantly, we show that specific inhibitors of nuclear transport prevent interaction with host transporters, and reduce HeV infection. These findings emphasize the critical role of host-virus interactions in HeV infection, and potential use of compounds targeting nuclear transport, such as the FDA-approved agent ivermectin, as anti-HeV agents.

Original languageEnglish
Article number358
Number of pages17
JournalScientific Reports
Volume8
Issue number1
DOIs
Publication statusPublished - 10 Jan 2018

Keywords

  • drug development
  • intrinsically disordered proteins
  • protein translocation
  • viral infection
  • PhD Scholarship

    Steven Heaton (Recipient), 2012

    Prize: Competitive Fellowships

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