Abstract
Ebola virus causes devastating hemorrhagic fever outbreaks for which no approved therapeutic exists. The viral nucleocapsid, which is minimally composed of the proteins NP, VP35, and VP24, represents an attractive target for drug development; however, the molecular determinants that govern the interactions and functions of these three proteins are still unknown. Through a series of mutational analyses, in combination with biochemical and bioinformatics approaches, we identified a region on VP24 that was critical for its interaction with NP. Importantly, we demonstrated that the interaction between VP24 and NP was required for both nucleocapsid assembly and genome packaging. Not only does this study underscore the critical role that these proteins play in the viral replication cycle, but it also identifies a key interaction interface on VP24 that may serve as a novel target for antiviral therapeutic intervention.
Highlights
Ebola virus (EBOV), which belongs to the family Filoviridae and the order Mononegavirales, is the causative agent of severe hemorrhagic fever in humans and has been responsible for several large outbreaks throughout Africa, with case fatality rates reaching as high as 90%1
Given the critical role played by NP, virion protein 35 (VP35), and VP24 in the formation of the EBOV nucleocapsid, we first sought to examine the interactions among these three proteins
Immunoprecipitation (IP) of cell lysates with an anti-FLAG antibody followed by Western blotting (WB) with an anti-Myc or anti-VP24 antibody demonstrated an interaction between NP and VP35 (Fig. 1a) and NP and VP24 (Fig. 1b), providing the clearest evidence so far reported that NP directly interacts with both VP35 and VP24 in the absence of any other viral protein[14, 20]
Summary
Ebola virus (EBOV), which belongs to the family Filoviridae and the order Mononegavirales, is the causative agent of severe hemorrhagic fever in humans and has been responsible for several large outbreaks throughout Africa, with case fatality rates reaching as high as 90%1. The viral nucleocapsid is among the most complex of all mononegaviruses, consisting of NP, which binds the viral genome, as well as VP35, VP30, VP24, and L12. Of these five proteins, only NP, VP35, and VP24 are required to produce structures that are morphologically indistinguishable from nucleocapsids observed during EBOV infection[13,14,15]. The identification of a discrete interaction interface on VP24—with a critical functional role—may provide a target for new and urgently needed antiviral drugs, the development of which has lagged well behind the development of vaccines
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
