Hendra virus V protein's plasticity enables it to bind to nuclear transport proteins

SC Atkinson1, MD Audsley1, DR Thomas1, GA Marsh2, JJ Paxman3, C Dogovski4, SM Heaton1, C Wang1, K Lieu1, KM Wagstaff1, GW Moseley4, DA Jans1 and NA Borg1

  1. Infection & Immunity Program, Monash Biomedicine Discovery Institute and Department of Biochemistry & Molecular Biology, Monash University, Clayton, Victoria, Australia
  2. CSIRO Health and Biosecurity, Australian Animal Health Laboratory (AAHL), Geelong, Victoria 2330, Australia
  3. La Trobe Institute for Molecular Sciences and Department of Biochemistry and Genetics, La Trobe University, Melbourne, VIC 3086, Australia
  4. Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, VIC 3010, Australia

Hendra virus (HeV) is a paramyxovirus that causes severe disease and a high incidence of fatality in infected humans. Despite recurrent outbreaks and potential for human lethality no vaccine or anti-viral agent is available to prevent or treat human HeV infection. Key to HeV pathogenicity is the viral phosphoprotein (P) gene, which also encodes the V and W proteins as distinct products. V modulates the host response to infection by targeting numerous host proteins. Here, by combining in vitro and in vivo analyses, we show nuclear transport receptors are amongst those targeted by HeV V, and play a role in infection. Structural analysis reveals HeV V is inherently disordered and gains structure upon binding its target nuclear transport receptors; a trait that offers numerous functional advantages. These findings broaden our understanding of HeV-host interactions.