The coronavirus proofreading exoribonuclease mediates extensive viral recombination

• DOI: 10.1371/journal.ppat.1009226
• Publication Date: 2021-01-19T18:51:22Z
• Authors: Jennifer Gribble; Laura J. Stevens; Maria L. Agostini; Jordan Anderson-D...; James D. Chappell; Xiaotao Lu; Andrea J. Pruijssers; Andrew L. Routh; Mark R. Denison
• Keywords: Exoribonuclease; Proofreading; Coronavirus; RNA virus

Recombination is proposed to be critical for coronavirus (CoV) diversity and emergence of SARS-CoV-2 other zoonotic CoVs. While RNA recombination required during normal CoV replication, the mechanisms determinants are not known. CoVs encode an proofreading exoribonuclease (nsp14-ExoN) that distinct from polymerase responsible high-fidelity synthesis, resistance nucleoside analogues, immune evasion, virulence. Here, we demonstrate CoVs, including SARS-CoV-2, MERS-CoV, model murine hepatitis virus (MHV), generate extensive diverse products replication in culture. We show MHV nsp14-ExoN native recombination, inactivation ExoN results decreased frequency altered products. These add yet another function nsp14-ExoN, highlight uniqueness evolved replicase, further emphasize as a central, completely conserved, vulnerable target inhibitors attenuation future emerging