The coronavirus proofreading exoribonuclease mediates extensive viral recombination.
PLoS Pathog
; 17(1): e1009226, 2021 01.
Article
en En
| MEDLINE
| ID: mdl-33465137
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.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Replicación Viral
/
Infecciones por Coronavirus
/
Exorribonucleasas
/
SARS-CoV-2
/
Tratamiento Farmacológico de COVID-19
Límite:
Humans
Idioma:
En
Revista:
PLoS Pathog
Año:
2021
Tipo del documento:
Article
País de afiliación:
Estados Unidos