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

Journal Article · · Nature Communications
DOI:https://doi.org/10.1038/ncomms15576· OSTI ID:1368315
 [1];  [2];  [3];  [2];  [3];  [2];  [3]
  1. Guangzhou Medical Univ. (China); Washington Univ. School of Medicine, St. Louis, MO (United States)
  2. Georgia State Univ., Atlanta, GA (United States)
  3. Washington Univ. School of Medicine, St. Louis, MO (United States)
+ Show Author Affiliations

Ebola virus (EBOV) is an enveloped negative-sense RNA virus that causes sporadic outbreaks with high case fatality rates. Ebola viral protein 30 (eVP30) plays a critical role in EBOV transcription initiation at the nucleoprotein (eNP) gene, with additional roles in the replication cycle such as viral assembly. However, the mechanistic basis for how eVP30 functions during the virus replication cycle is currently unclear. Here we define a key interaction between eVP30 and a peptide derived from eNP that is important to facilitate interactions leading to the recognition of the RNA template. We present crystal structures of the eVP30 C-terminus in complex with this eNP peptide. Functional analyses of the eVP30–eNP interface identify residues that are critical for viral RNA synthesis. Altogether, these results support a model where the eVP30–eNP interaction plays a critical role in transcription initiation and provides a novel target for the development of antiviral therapy.

Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (United States)
Sponsoring Organization:
USDOE; National Institutes of Health (NIH); Dept. of the Defense, Defense Threat Reduction Agency
Grant/Contract Number:
AC02-06CH11357; R01AI107056; R01AI123926; P01AI120943; R01AI114654; U191099565; U19AI109945; U19AI109664; HDTRA1-14-0013; HDTRA1-12-1-0051
OSTI ID:
1368315
Journal Information:
Nature Communications, Vol. 8, Issue 1; ISSN 2041-1723
Publisher:
Nature Publishing GroupCopyright Statement
Country of Publication:
United States
Language:
ENGLISH
Citation Metrics:
Cited by: 28 works
Citation information provided by
Web of Science

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Cited By (3)

Conformational Selection of a Polyproline Peptide by Ebola Virus VP30 journal October 2018
Host factor SMYD3 is recruited by Ebola virus nucleoprotein to facilitate viral mRNA transcription journal January 2019
Serine-Arginine Protein Kinase 1 Regulates Ebola Virus Transcription journal February 2020

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59 BASIC BIOLOGICAL SCIENCES
Ebola virus
Viral infection
X-ray crystallography