About: Infidelity of SARS-CoV Nsp14-Exonuclease Mutant Virus Replication Is Revealed by Complete Genome Sequencing

Facets (new session)
Description
Metadata
Settings
- owl:sameAs
- Inference Rule:

About: Infidelity of SARS-CoV Nsp14-Exonuclease Mutant Virus Replication Is Revealed by Complete Genome Sequencing Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : wasabi.inria.fr associated with source document(s)

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	Infidelity of SARS-CoV Nsp14-Exonuclease Mutant Virus Replication Is Revealed by Complete Genome Sequencing
Creator	Halpin, Rebecca Spiro, David Baric, Ralph Lu, Xiaotao Li, Kelvin Venter, Eli Scherbakova, Sana Denison, Mark Becker, Michelle Eckerle, Lance Graham, Rachel Stockwell, Timothy
Source	Medline; PMC
abstract	Most RNA viruses lack the mechanisms to recognize and correct mutations that arise during genome replication, resulting in quasispecies diversity that is required for pathogenesis and adaptation. However, it is not known how viruses encoding large viral RNA genomes such as the Coronaviridae (26 to 32 kb) balance the requirements for genome stability and quasispecies diversity. Further, the limits of replication infidelity during replication of large RNA genomes and how decreased fidelity impacts virus fitness over time are not known. Our previous work demonstrated that genetic inactivation of the coronavirus exoribonuclease (ExoN) in nonstructural protein 14 (nsp14) of murine hepatitis virus results in a 15-fold decrease in replication fidelity. However, it is not known whether nsp14-ExoN is required for replication fidelity of all coronaviruses, nor the impact of decreased fidelity on genome diversity and fitness during replication and passage. We report here the engineering and recovery of nsp14-ExoN mutant viruses of severe acute respiratory syndrome coronavirus (SARS-CoV) that have stable growth defects and demonstrate a 21-fold increase in mutation frequency during replication in culture. Analysis of complete genome sequences from SARS-ExoN mutant viral clones revealed unique mutation sets in every genome examined from the same round of replication and a total of 100 unique mutations across the genome. Using novel bioinformatic tools and deep sequencing across the full-length genome following 10 population passages in vitro, we demonstrate retention of ExoN mutations and continued increased diversity and mutational load compared to wild-type SARS-CoV. The results define a novel genetic and bioinformatics model for introduction and identification of multi-allelic mutations in replication competent viruses that will be powerful tools for testing the effects of decreased fidelity and increased quasispecies diversity on viral replication, pathogenesis, and evolution.
has issue date	2010-05-06(xsd:dateTime)
bibo:doi	10.1371/journal.ppat.1000896
bibo:pmid	20463816
has license	cc-by
sha1sum (hex)	e4007988dba3dcfa65314d50324bdff1ba7f55c2
schema:url	https://doi.org/10.1371/journal.ppat.1000896
resource representing a document's title	Infidelity of SARS-CoV Nsp14-Exonuclease Mutant Virus Replication Is Revealed by Complete Genome Sequencing
has PubMed Central identifier	PMC2865531
has PubMed identifier	20463816
schema:publication	PLoS Pathog
resource representing a document's body	covid:e4007988dba3dcfa65314d50324bdff1ba7f55c2#body_text
is schema:about of	named entity 'viruses' named entity 'compared' named entity 'sequences' named entity 'Further' named entity 'stable' named entity 'quasispecies' named entity 'genome' named entity 'wild-type' named entity 'replication' named entity 'Most' named entity 'mutation' named entity 'Mutant' named entity 'HAVE' named entity 'INCREASED' named entity 'IN VITRO' named entity 'COMPLETE' named entity 'REVEALED' named entity 'POWERFUL' named entity 'MECHANISMS' named entity 'NOVEL' named entity 'SEQUENCES' named entity 'PROTEIN ' named entity 'LIMITS' named entity 'CORONAVIRUSES' named entity 'STABLE' named entity 'SARS-COV' named entity 'PREVIOUS' named entity 'INFIDELITY' covid:arg/e4007988dba3dcfa65314d50324bdff1ba7f55c2 named entity 'RETENTION' named entity 'CLONES' named entity 'RECOVERY' named entity 'MODEL' named entity 'ENGINEERING' named entity 'RESULTS' named entity 'FOLD INCREASE' named entity 'POPULATION' named entity 'GENOMES' named entity 'REPLICATION' named entity 'RECOGNIZE' named entity 'USING' named entity 'TOOLS' named entity 'LOAD' named entity 'DEEP SEQUENCING' named entity 'INFIDELITY' named entity 'LARGE' named entity 'REQUIRED' named entity 'GROWTH' named entity 'MUTANT' named entity 'SARS-COV' named entity 'EXONUCLEASE' named entity 'BALANCE' named entity 'SEVERE ACUTE RESPIRATORY SYNDROME CORONAVIRUS' named entity 'VIRUSES' named entity 'CONTINUED' named entity 'IMPACT' named entity 'QUASISPECIES' named entity 'MULTI' named entity 'VIRAL REPLICATION' named entity 'CORRECT' named entity 'INTRODUCTION' named entity 'DIVERSITY' named entity 'HOW' named entity 'NOT KNOWN' named entity 'IMPACTS' named entity 'ADAPTATION' named entity 'MUTATION FREQUENCY' named entity 'RNA' named entity 'EXON' named entity 'BIOINFORMATIC'

Faceted Search & Find service v1.13.91 as of Mar 24 2020

Alternative Linked Data Documents: Sponger | ODE Content Formats:

RDF

ODATA

Microdata

About

OpenLink Virtuoso version 07.20.3229 as of Jul 10 2020, on Linux (x86_64-pc-linux-gnu), Single-Server Edition (94 GB total memory)
Data on this page belongs to its respective rights holders.
Virtuoso Faceted Browser Copyright © 2009-2024 OpenLink Software