{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Graham RL"],"funding":["NIAID NIH HHS"],"pagination":["1820-6"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC3518599"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["18(12)"],"pubmed_abstract":["Live, attenuated RNA virus vaccines are efficacious but subject to reversion to virulence. Among RNA viruses, replication fidelity is recognized as a key determinant of virulence and escape from antiviral therapy; increased fidelity is attenuating for some viruses. Coronavirus (CoV) replication fidelity is approximately 20-fold greater than that of other RNA viruses and is mediated by a 3'→5' exonuclease (ExoN) activity that probably functions in RNA proofreading. In this study we demonstrate that engineered inactivation of severe acute respiratory syndrome (SARS)-CoV ExoN activity results in a stable mutator phenotype with profoundly decreased fidelity in vivo and attenuation of pathogenesis in young, aged and immunocompromised mice. The ExoN inactivation genotype and mutator phenotype ar"],"journal":["Nature medicine"],"pubmed_title":["A live, impaired-fidelity coronavirus vaccine protects in an aged, immunocompromised mouse model of lethal disease."],"pmcid":["PMC3518599"],"funding_grant_id":["F32 AI080148","AI075297","5F32AI080148","U54-AI057157","R01 AI075297","HHSN272200900007C","U54 AI057157"],"pubmed_authors":["Graham RL","Denison MR","Baric RS","Becker MM","Bolles M","Eckerle LD"],"additional_accession":[]},"is_claimable":false,"name":"A live, impaired-fidelity coronavirus vaccine protects in an aged, immunocompromised mouse model of lethal disease.","description":"Live, attenuated RNA virus vaccines are efficacious but subject to reversion to virulence. Among RNA viruses, replication fidelity is recognized as a key determinant of virulence and escape from antiviral therapy; increased fidelity is attenuating for some viruses. Coronavirus (CoV) replication fidelity is approximately 20-fold greater than that of other RNA viruses and is mediated by a 3'→5' exonuclease (ExoN) activity that probably functions in RNA proofreading. In this study we demonstrate that engineered inactivation of severe acute respiratory syndrome (SARS)-CoV ExoN activity results in a stable mutator phenotype with profoundly decreased fidelity in vivo and attenuation of pathogenesis in young, aged and immunocompromised mice. The ExoN inactivation genotype and mutator phenotype ar","dates":{"release":"2012-01-01T00:00:00Z","publication":"2012 Dec","modification":"2025-04-04T11:02:37.753Z","creation":"2019-03-27T01:01:39Z"},"accession":"S-EPMC3518599","cross_references":{"pubmed":["23142821"],"doi":["10.1038/nm.2972"]}}