{"doi":"10.1128/jvi.01734-19","title":"Structure-Guided Mutagenesis Alters Deubiquitinating Activity and Attenuates Pathogenesis of a Murine Coronavirus","abstract":"Coronaviruses employ a genetic economy by encoding multifunctional proteins that function in viral replication and also modify the host environment to disarm the innate immune response. The coronavirus papain-like protease 2 (PLP2) domain possesses protease activity, which cleaves the viral replicase polyprotein, and also DUB activity (deconjugating ubiquitin/ubiquitin-like molecules from modified substrates) using identical catalytic residues. To separate the DUB activity from the protease activity, we employed a structure-guided mutagenesis approach and identified residues that are important for ubiquitin binding. We found that mutating the ubiquitin-binding residues results in a PLP2 that has reduced DUB activity but retains protease activity. We engineered a recombinant murine coronavirus to express the DUB mutant and showed that the DUB mutant virus activated an earlier type I interferon response in macrophages and exhibited reduced replication in mice. The results of this study demonstrate that PLP2/DUB is an interferon antagonist and a virulence trait of coronaviruses.","journal":"Journal of Virology","year":2020,"id":101362,"datarank":0.49983067652628066,"base_score":3.332204510175204,"endowment":3.332204510175204,"self_citation_contribution":0.49983067652628066,"citation_network_contribution":0.0,"self_endowment_contribution":0.49983067652628066,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":27,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9569,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":496183,"name":"Yafang Chen","orcid":"0000-0001-5909-1419","position":1,"is_corresponding":false},{"id":496832,"name":"Anna M. Mielech","orcid":null,"position":2,"is_corresponding":false},{"id":233692,"name":"Matthew Hackbart","orcid":"0000-0001-6244-6292","position":3,"is_corresponding":false},{"id":404418,"name":"Kristina R. Kesely","orcid":"0000-0002-8828-7573","position":4,"is_corresponding":false},{"id":496184,"name":"Robert C. Mettelman","orcid":"0000-0002-3527-5616","position":5,"is_corresponding":false},{"id":462694,"name":"Amornrat O’Brien","orcid":null,"position":6,"is_corresponding":false},{"id":107926,"name":"Mackenzie E. Chapman","orcid":"0000-0001-9969-2446","position":7,"is_corresponding":false},{"id":107929,"name":"Andrew D. Mesecar","orcid":"0000-0002-1241-2577","position":8,"is_corresponding":false},{"id":77531,"name":"Susan C. Baker","orcid":"0000-0001-6485-8143","position":9,"is_corresponding":false},{"id":233693,"name":"Xufang Deng","orcid":"0000-0002-7604-3627","position":0,"is_corresponding":true}],"reference_count":44,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T22:39:38.259162Z","pmid":"32188728","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":[]}