Oct 29, 2018

Reporter assays for Ebola virus nucleoprotein oligomerization, virion-like particle budding, and minigenome activity reveal the importance of nucleoprotein amino acid position 111

BioRxiv : the Preprint Server for Biology
Aaron E LinPardis C Sabeti

Abstract

For highly pathogenic viruses, reporter assays that can be rapidly performed are critically needed to identify potentially functional mutations for further study under maximal containment (e.g., biosafety level 4 [BSL-4]). The Ebola virus nucleoprotein (NP) plays multiple essential roles during the viral life cycle, yet few tools exist to study the protein under BSL-2 or equivalent containment. Therefore, we adapted reporter assays to measure NP oligomerization and virion-like particle (VLP) production in live cells and further measure transcription and replication using established minigenome assays. As a proof-of-concept, we examined the NP-R111C substitution, which emerged during the 2013‒2016 Western African Ebola virus disease epidemic and rose to high frequency. NP-R111C slightly increased NP oligomerization and VLP budding but slightly decreased transcription and replication. By contrast, a synthetic charge-reversal mutant, NP-R111E, greatly increased oligomerization but abrogated transcription and replication. These results are intriguing in light of recent structures of NP oligomers, which reveal that the neighboring residue, K110, forms a salt bridge with E349 on adjacent NP molecules. By developing and utilizing mult...Continue Reading

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Mentioned in this Paper

JUN gene
Study
JUND gene
Hemorrhagic Fever, Ebola
Ebola virus
Nucleoproteins
Ebolavirus
Virion
Transcription, Genetic
Virus Replication

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