Portal de Periódicos da CAPES

The coronavirus proofreading exoribonuclease mediates extensive viral recombination

2021; Public Library of Science; Volume: 17; Issue: 1 Linguagem: Inglês

10.1371/journal.ppat.1009226

1553-7374

Jennifer Gribble, Laura J. Stevens, Maria L. Agostini, Jordan Anderson-Daniels, James D. Chappell, Xiaotao Lu, Andrea J. Pruijssers, Andrew Routh, Mark R. Denison,

SARS-CoV-2 and COVID-19 Research

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.