Reactome | Infidelity of SARS-CoV Nsp14-exonuclease mutant virus replication is revealed by complete genome sequencing

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Infidelity of SARS-CoV Nsp14-exonuclease mutant virus replication is revealed by complete genome sequencing Show undefined attributes

author	[Person:9682596] Eckerle, LD [Person:9682589] Becker, MM [Person:9682592] Halpin, RA [Person:1614119] Li, K [Person:9682594] Venter, E [Person:9680280] Lu, X [Person:9682590] Scherbakova, S [Person:9680267] Graham, RL [Person:9614514] Baric, RS [Person:9682593] Stockwell, TB [Person:9682595] Spiro, DJ [Person:9680281] Denison, MR
created	[InstanceEdit:9682591] Orlic-Milacic, Marija, 2020-04-13
dbId	9682597
displayName	Infidelity of SARS-CoV Nsp14-exonuclease mutant virus replication is revealed by complete genome sequencing
journal	PLoS Pathog.
pages	e1000896
pubMedIdentifier	20463816
schemaClass	LiteratureReference
title	Infidelity of SARS-CoV Nsp14-exonuclease mutant virus replication is revealed by complete genome sequencing
url	http://www.ncbi.nlm.nih.gov/pubmed/20463816
volume	6
year	2010

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[Summation:9694346] This COVID-19 event has been created by a combination of computational inference (see https://reactome.org/documentation/inferred-events) from SARS-CoV-1 data and manual curation, as described in the summation for the overall SARS-CoV-2 infection pathway.

In the presence of functional nsp14, which acts as a 3'-to-5' exonuclease, the mutation rate during human SARS coronavirus 1 (SARS-CoV-1) replication is 9 x 10^-7 (9E-7) per nucleotide per replication cycle or 2.2 x 10^-5 (2.2E-5) non-redundant substitutions per nucleotide, which translates into 2-3 nucleotide substitutions for each replicated SARS-CoV-1 genome. When nsp14 is defective, the mutation rate during SARS-CoV-1 replication increases to 1.2 x 10^-5 (1.2E-5) mutations per nucleotide per replication cycle or 3.34 x 10^-4 (3.34E-4) non-redundant substitutions per nucleotide, which translates into 12-23 nucleotide substitutions for each replicated SARS-CoV-1 genome (Eckerle et al. 2010). Here the process is annotated in two steps, nsp12- mediated misincorporation of a base (this reaction) and nsp14-mediated detection and removal of that base (next reaction).
[Reaction:R-HSA-9682603] nsp14 acts as a 3'-to-5' exonuclease to remove misincorporated nucleotides from nascent RNA
[BlackBoxEvent:R-HSA-9682563] nsp12 misincorporates a nucleotide in nascent RNA minus strand
[Summation:9694564] In human SARS coronavirus 2 (SARS-CoV-2) nsp14 is essential ...

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