{"doi":"10.1371/journal.ppat.1009226","title":"The coronavirus proofreading exoribonuclease mediates extensive viral recombination","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.","journal":"PLoS Pathogens","year":2021,"id":145920,"datarank":0.850998490075724,"base_score":5.673323267171493,"endowment":5.673323267171493,"self_citation_contribution":0.850998490075724,"citation_network_contribution":0.0,"self_endowment_contribution":0.850998490075724,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":290,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9607,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":105604,"name":"Laura J. Stevens","orcid":"0000-0003-4386-6958","position":1,"is_corresponding":false},{"id":229402,"name":"Maria L. Agostini","orcid":null,"position":2,"is_corresponding":false},{"id":552567,"name":"Jordan Anderson-Daniels","orcid":"0000-0002-9275-4330","position":3,"is_corresponding":false},{"id":105611,"name":"James D. Chappell","orcid":"0000-0002-7382-7864","position":4,"is_corresponding":false},{"id":226331,"name":"Xiaotao Lu","orcid":"0000-0001-9935-1713","position":5,"is_corresponding":false},{"id":218074,"name":"Andrea J. Pruijssers","orcid":"0000-0001-7910-626X","position":6,"is_corresponding":false},{"id":275508,"name":"Andrew Routh","orcid":"0000-0002-2874-5990","position":7,"is_corresponding":false},{"id":105126,"name":"Mark R. Denison","orcid":"0000-0003-2655-0900","position":8,"is_corresponding":false},{"id":552566,"name":"Jennifer Gribble","orcid":"0000-0003-0815-5798","position":0,"is_corresponding":true}],"reference_count":77,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:42:12.871665Z","pmid":"33465137","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}