skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Ebola virus VP30 and nucleoprotein interactions modulate viral RNA synthesis

Authors:
; ; ; ; ; ;
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
DODNIH
OSTI Identifier:
1368315
Resource Type:
Journal Article
Resource Relation:
Journal Name: Nature Communications; Journal Volume: 8; Journal Issue: 06, 2017
Country of Publication:
United States
Language:
ENGLISH

Citation Formats

Xu, Wei, Luthra, Priya, Wu, Chao, Batra, Jyoti, Leung, Daisy W., Basler, Christopher F., and Amarasinghe, Gaya K. Ebola virus VP30 and nucleoprotein interactions modulate viral RNA synthesis. United States: N. p., 2017. Web. doi:10.1038/ncomms15576.
Xu, Wei, Luthra, Priya, Wu, Chao, Batra, Jyoti, Leung, Daisy W., Basler, Christopher F., & Amarasinghe, Gaya K. Ebola virus VP30 and nucleoprotein interactions modulate viral RNA synthesis. United States. doi:10.1038/ncomms15576.
Xu, Wei, Luthra, Priya, Wu, Chao, Batra, Jyoti, Leung, Daisy W., Basler, Christopher F., and Amarasinghe, Gaya K. Thu . "Ebola virus VP30 and nucleoprotein interactions modulate viral RNA synthesis". United States. doi:10.1038/ncomms15576.
@article{osti_1368315,
title = {Ebola virus VP30 and nucleoprotein interactions modulate viral RNA synthesis},
author = {Xu, Wei and Luthra, Priya and Wu, Chao and Batra, Jyoti and Leung, Daisy W. and Basler, Christopher F. and Amarasinghe, Gaya K.},
abstractNote = {},
doi = {10.1038/ncomms15576},
journal = {Nature Communications},
number = 06, 2017,
volume = 8,
place = {United States},
year = {Thu Jun 08 00:00:00 EDT 2017},
month = {Thu Jun 08 00:00:00 EDT 2017}
}
  • During viral RNA synthesis, Ebola virus (EBOV) nucleoprotein (NP) alternates between an RNA-template-bound form and a template-free form to provide the viral polymerase access to the RNA template. In addition, newly synthesized NP must be prevented from indiscriminately binding to noncognate RNAs. Here, we investigate the molecular bases for these critical processes. We identify an intrinsically disordered peptide derived from EBOV VP35 (NPBP, residues 20–48) that binds NP with high affinity and specificity, inhibits NP oligomerization, and releases RNA from NP-RNA complexes in vitro. The structure of the NPBP/ΔNP NTD complex, solved to 3.7 Å resolution, reveals how NPBP peptidemore » occludes a large surface area that is important for NP-NP and NP-RNA interactions and for viral RNA synthesis. Together, our results identify a highly conserved viral interface that is important for EBOV replication and can be targeted for therapeutic development.« less
  • Filoviruses are capable of causing deadly hemorrhagic fevers. All nonsegmented negative-sense RNA-virus nucleocapsids are composed of a nucleoprotein (NP), a phosphoprotein (VP35) and a polymerase (L). However, the VP30 RNA-synthesis co-factor is unique to the filoviruses. The assembly, structure, and function of the filovirus RNA replication complex remain unclear. Here, we have characterized the interactions of Ebola, Sudan and Marburg virus VP30 with NP using in vitro biochemistry, structural biology and cell-based mini-replicon assays. We have found that the VP30 C-terminal domain interacts with a short peptide in the C-terminal region of NP. Further, we have solved crystal structures ofmore » the VP30-NP complex for both Ebola and Marburg viruses. These structures reveal that a conserved, proline-rich NP peptide binds a shallow hydrophobic cleft on the VP30 C-terminal domain. Structure-guided Ebola virus VP30 mutants have altered affinities for the NP peptide. Correlation of these VP30-NP affinities with the activity for each of these mutants in a cell-based mini-replicon assay suggests that the VP30-NP interaction plays both essential and inhibitory roles in Ebola virus RNA synthesis.« less
  • Ebola virus VP35 inhibits alpha/beta interferon production and functions as a viral polymerase cofactor. Previously, the 8-kDa cytoplasmic dynein light chain (LC8) was demonstrated to interact with VP35, but the functional consequences were unclear. Here we demonstrate that the interaction is direct and of high affinity and that binding stabilizes the VP35 N-terminal oligomerization domain and enhances viral RNA synthesis. Mutational analysis demonstrates that VP35 interaction is required for the functional effects of LC8.