Ebola virus VP30 and nucleoprotein interactions modulate viral RNA synthesis

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 vira...

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Veröffentlicht in:Nature communications Jg. 8; H. 1; S. 15576 - 11
Hauptverfasser: Xu, Wei, Luthra, Priya, Wu, Chao, Batra, Jyoti, Leung, Daisy W., Basler, Christopher F., Amarasinghe, Gaya K.
Format: Journal Article
Sprache:Englisch
Veröffentlicht: London Nature Publishing Group UK 08.06.2017
Nature Publishing Group
Nature Portfolio
Schlagworte:
631/326/596/2042
631/535/1266
692/699/255/2514
BASIC BIOLOGICAL SCIENCES
Chromatography
Ebola virus
Epidemics
Fatalities
Humanities and Social Sciences
multidisciplinary
Mutation
Peptides
Proteins
Science
Science (multidisciplinary)
Viral infection
X-ray crystallography
United States > US
Georgia
ISSN:2041-1723, 2041-1723
Online-Zugang:Volltext
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Zusammenfassung: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. Ebola virus (EBOV) VP30 is a multifunctional protein that plays a role in transcription, but molecular details remain unknown. Here, using X-ray crystallography and minigenome assays, Xu et al . define the interaction between VP30 and a portion of NP that is critical for optimal EBOV RNA synthesis.
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USDOE
Dept. of the Defense, Defense Threat Reduction Agency
AC02-06CH11357; R01AI107056; R01AI123926; P01AI120943; R01AI114654; U191099565; U19AI109945; U19AI109664; HDTRA1-14-0013; HDTRA1-12-1-0051
National Institutes of Health (NIH)
Present address: State Key Lab of Respiratory Disease, Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou 510060, China
ISSN:2041-1723
2041-1723
DOI:10.1038/ncomms15576