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The coronavirus proofreading exoribonuclease mediates extensive viral recombination
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The coronavirus proofreading exoribonuclease mediates extensive viral recombination
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Journal Article
The coronavirus proofreading exoribonuclease mediates extensive viral recombination
2021
Overview
Recombination is proposed to be critical for coronavirus (CoV) diversity and emergence of SARS-CoV-2 and other zoonotic CoVs. While RNA recombination is required during normal CoV replication, the mechanisms and determinants of CoV recombination are not known. CoVs encode an RNA proofreading exoribonuclease (nsp14-ExoN) that is distinct from the CoV polymerase and is responsible for high-fidelity RNA synthesis, resistance to nucleoside analogues, immune evasion, and virulence. Here, we demonstrate that CoVs, including SARS-CoV-2, MERS-CoV, and the model CoV murine hepatitis virus (MHV), generate extensive and diverse recombination products during replication in culture. We show that the MHV nsp14-ExoN is required for native recombination, and that inactivation of ExoN results in decreased recombination frequency and altered recombination products. These results add yet another critical function to nsp14-ExoN, highlight the uniqueness of the evolved coronavirus replicase, and further emphasize nsp14-ExoN as a central, completely conserved, and vulnerable target for inhibitors and attenuation of SARS-CoV-2 and future emerging zoonotic CoVs.
Publisher
Public Library of Science,Public Library of Science (PLoS)
Subject
Antiviral Agents - pharmacology
/ Coronavirus Infections - drug therapy
/ Coronavirus Infections - virology
/ COVID-19
/ Editing
/ Exoribonucleases - pharmacology
/ Humans
/ Medicine and health sciences
/ Middle East respiratory syndrome
/ Recombination, Genetic - drug effects
/ Research and analysis methods
/ RNA
/ Severe acute respiratory syndrome
/ Severe acute respiratory syndrome coronavirus 2
/ Vaccines
/ Viral Nonstructural Proteins - genetics
/ Virus Replication - drug effects
/ Virus Replication - genetics
/ Viruses
