The coronavirus proofreading exoribonuclease mediates extensive viral recombination.

Autor: Gribble J; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America.; Vanderbilt Institute for Infection, Immunology, and Inflammation (VI4), Vanderbilt University Medical Center, Nashville, Tennessee, United States of America., Stevens LJ; Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America., Agostini ML; Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America., Anderson-Daniels J; Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America., Chappell JD; Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America., Lu X; Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America., Pruijssers AJ; Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America., Routh AL; Department of Biochemistry and Molecular Biology, University of Texas-Medical Branch, Galveston, Texas, United States of America.; Sealy Center for Structural Biology and Molecular Biophysics, University of Texas-Medical Branch, Galveston, Texas, United States of America., Denison MR; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America.; Vanderbilt Institute for Infection, Immunology, and Inflammation (VI4), Vanderbilt University Medical Center, Nashville, Tennessee, United States of America.; Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America.
Jazyk: angličtina
Zdroj: PLoS pathogens [PLoS Pathog] 2021 Jan 19; Vol. 17 (1), pp. e1009226. Date of Electronic Publication: 2021 Jan 19 (Print Publication: 2021).
DOI: 10.1371/journal.ppat.1009226
Abstrakt: 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.
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
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