tetano
Editor, Senior Moderator
PLoS Pathog
. 2021 Jan 19;17(1):e1009226.
doi: 10.1371/journal.ppat.1009226. Online ahead of print.
The coronavirus proofreading exoribonuclease mediates extensive viral recombination
Jennifer Gribble[SUP] 1 2 [/SUP], Laura J Stevens[SUP] 3 [/SUP], Maria L Agostini[SUP] 3 [/SUP], Jordan Anderson-Daniels[SUP] 3 [/SUP], James D Chappell[SUP] 3 [/SUP], Xiaotao Lu[SUP] 3 [/SUP], Andrea J Pruijssers[SUP] 3 [/SUP], Andrew L Routh[SUP] 4 5 [/SUP], Mark R Denison[SUP] 1 2 3 [/SUP]
Affiliations
Abstract
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.
. 2021 Jan 19;17(1):e1009226.
doi: 10.1371/journal.ppat.1009226. Online ahead of print.
The coronavirus proofreading exoribonuclease mediates extensive viral recombination
Jennifer Gribble[SUP] 1 2 [/SUP], Laura J Stevens[SUP] 3 [/SUP], Maria L Agostini[SUP] 3 [/SUP], Jordan Anderson-Daniels[SUP] 3 [/SUP], James D Chappell[SUP] 3 [/SUP], Xiaotao Lu[SUP] 3 [/SUP], Andrea J Pruijssers[SUP] 3 [/SUP], Andrew L Routh[SUP] 4 5 [/SUP], Mark R Denison[SUP] 1 2 3 [/SUP]
Affiliations
- PMID: 33465137
- DOI: 10.1371/journal.ppat.1009226
Abstract
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.