title: Elucidation of the Cellular Interactome of Ebola Virus Nucleoprotein and Identification of Therapeutic Targets.
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.
authors: Institute of Infection and Global Health, University of Liverpool , Liverpool L3 5RF, U.K.|NIHR Health Protection Research Unit in Emerging and Zoonotic Infections , Liverpool L69 3GL, U.K.
authors: Isabel
authors: I
authors: García-Dorival
authors: Institute of Infection and Global Health, University of Liverpool , Liverpool L3 5RF, U.K.
authors: Weining
authors: W
authors: Wu
authors: Institute of Infection and Global Health, University of Liverpool , Liverpool L3 5RF, U.K.|NIHR Health Protection Research Unit in Emerging and Zoonotic Infections , Liverpool L69 3GL, U.K.
authors: Stuart D
authors: SD
authors: Armstrong
authors: School of Molecular and Cellular Biology, Faculty of Biological Science, University of Leeds , Leeds LS2 9JT, U.K.
authors: John N
authors: JN
authors: Barr
authors: NIHR Health Protection Research Unit in Emerging and Zoonotic Infections , Liverpool L69 3GL, U.K.|Public Health England , Porton Down, Salisbury SP4 0JG, U.K.
authors: Miles W
authors: MW
authors: Carroll
authors: Public Health England , Porton Down, Salisbury SP4 0JG, U.K.
authors: Roger
authors: R
authors: Hewson
authors: Institute of Infection and Global Health, University of Liverpool , Liverpool L3 5RF, U.K.|NIHR Health Protection Research Unit in Emerging and Zoonotic Infections , Liverpool L69 3GL, U.K.
authors: Julian A
authors: JA
authors: Hiscox
mesh_terms: D029043:Ebolavirus / Q000502:physiology*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D018832:Molecular Chaperones / Q000378:metabolism*; D058990:Molecular Targeted Therapy / Q000379:methods; D009698:Nucleoproteins / Q000737:chemistry / Q000378:metabolism*; D055550:Protein Stability; D011533:Proviruses; D012367:RNA, Viral / Q000096:biosynthesis; D014764:Viral Proteins / Q000378:metabolism; D014779:Virus Replication
chemical_list: D018840:HSP70 Heat-Shock Proteins; D018832:Molecular Chaperones; D009698:Nucleoproteins; D012367:RNA, Viral; D014764:Viral Proteins
keywords: Ebola virus; HSP70; inhibitor; interactome; label-free proteomics; nucleoprotein