Ebola virus VP30 and nucleoprotein interactions modulate viral RNA synthesis
Abstract
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.
- Authors:
-
- Guangzhou Medical Univ. (China); Washington Univ. School of Medicine, St. Louis, MO (United States)
- Georgia State Univ., Atlanta, GA (United States)
- Washington Univ. School of Medicine, St. Louis, MO (United States)
- Publication Date:
- Research Org.:
- Argonne National Laboratory (ANL), Argonne, IL (United States)
- Sponsoring Org.:
- USDOE; National Institutes of Health (NIH); Dept. of the Defense, Defense Threat Reduction Agency
- OSTI Identifier:
- 1368315
- Grant/Contract Number:
- AC02-06CH11357; R01AI107056; R01AI123926; P01AI120943; R01AI114654; U191099565; U19AI109945; U19AI109664; HDTRA1-14-0013; HDTRA1-12-1-0051
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Nature Communications
- Additional Journal Information:
- Journal Volume: 8; Journal Issue: 1; Journal ID: ISSN 2041-1723
- Publisher:
- Nature Publishing Group
- Country of Publication:
- United States
- Language:
- ENGLISH
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; Ebola virus; Viral infection; X-ray crystallography
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. https://doi.org/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. https://doi.org/10.1038/ncomms15576. https://www.osti.gov/servlets/purl/1368315.
@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 = {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.},
doi = {10.1038/ncomms15576},
journal = {Nature Communications},
number = 1,
volume = 8,
place = {United States},
year = {Thu Jun 08 00:00:00 EDT 2017},
month = {Thu Jun 08 00:00:00 EDT 2017}
}
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Works referencing / citing this record:
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