Elucidation of the Cellular Interactome of Ebola Virus Nucleoprotein and Identification of Therapeutic Targets

Isabel García-Dorival, Weining Wu, Stuart D. Armstrong, John N. Barr, Miles Carroll, Roger Hewson, Julian A. Hiscox

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)

Abstract

Ebola virus (EBOV) infection results in severe disease and in some cases lethal hemorrhagic fever. The infection is directed by seven viral genes that encode nine viral proteins. By definition, viruses are obligate intracellular parasites and require aspects of host cell biology in order to replicate their genetic material, assemble new virus particles, and subvert host cell antiviral responses. Currently licensed antivirals are targeted against viral proteins to inhibit their function. However, experience with treating HIV and influenza virus demonstrates that resistant viruses are soon selected. An emerging area in virology is to transiently target host cell proteins that play critical proviral roles in virus biology, especially for acute infections. This has the advantage that the protein being targeted is evolutionary removed from the genome of the virus. Proteomics can aid in discovery biology and identify cellular proteins that may be utilized by the virus to facilitate infection. This work focused on defining the interactome of the EBOV nucleoprotein and identified that cellular chaperones, including HSP70, associate with this protein to promote stability. Utilization of a mini-genome replication system based on a recent Makona isolate demonstrated that disrupting the stability of NP had an adverse effect on viral RNA synthesis.

Original languageEnglish
Pages (from-to)4290-4303
Number of pages14
JournalJournal of Proteome Research
Volume15
Issue number12
DOIs
Publication statusPublished - 2 Dec 2016

Keywords

  • Ebola virus
  • HSP70
  • inhibitor
  • interactome
  • label-free proteomics
  • nucleoprotein

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