{"doi":"10.1128/jvi.00834-19","title":"Tyr82 Amino Acid Mutation in PB1 Polymerase Induces an Influenza Virus Mutator Phenotype","abstract":"<jats:p>\n            Influenza A virus rapidly acquires antigenic changes and antiviral drug resistance, which limit the effectiveness of vaccines and drug treatments, primarily owing to its high rate of evolution. Virus populations formed by quasispecies can contain resistance mutations even before a selective pressure is applied. To study the effects of the viral mutation spectrum and quasispecies, high- and low-fidelity variants have been isolated for several RNA viruses. Here, we report the discovery of a low-fidelity RdRp variant of influenza A virus that contains a substitution at Tyr82 in PB1. Viruses containing the PB1-Y82C substitution showed growth kinetics and viral RNA synthesis levels similar to those of the wild-type virus in cell culture; however, they had significantly attenuated phenotypes in a chicken egg infection experiment. These data demonstrated that decreased RdRp fidelity attenuates influenza A virus\n            <jats:italic>in vivo</jats:italic>\n            , which is a desirable feature for the development of safer live attenuated vaccine candidates.\n          </jats:p>","journal":"Journal of Virology","year":2019,"id":595123,"datarank":0.29188652235829704,"base_score":1.9459101490553132,"endowment":1.9459101490553132,"self_citation_contribution":0.29188652235829704,"citation_network_contribution":0.0,"self_endowment_contribution":0.29188652235829704,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1329569,"name":"Kazumasa Shirai","orcid":"0009-0002-3144-8230","position":1,"is_corresponding":false},{"id":1523761,"name":"Kotaro Mori","orcid":null,"position":2,"is_corresponding":false},{"id":1523762,"name":"Hidetaka Muratsu","orcid":null,"position":3,"is_corresponding":false},{"id":1523763,"name":"Hiroshi Ushirogawa","orcid":null,"position":4,"is_corresponding":false},{"id":1523764,"name":"Ryosuke L. Ohniwa","orcid":null,"position":5,"is_corresponding":false},{"id":74172,"name":"Kousuke Hanada","orcid":"0000-0001-8854-4261","position":6,"is_corresponding":false},{"id":1523765,"name":"Mineki Saito","orcid":null,"position":7,"is_corresponding":false},{"id":141779,"name":"Tadasuke Naito","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Tyr82 Amino Acid Mutation in PB1 Polymerase Induces an Influenza Virus Mutator Phenotype","abstract":"Influenza A virus rapidly acquires antigenic changes and antiviral drug resistance, which limit the effectiveness of vaccines and drug treatments, primarily owing to its high rate of evolution. Virus populations formed by quasispecies can contain resistance mutations even before a selective pressure is applied. To study the effects of the viral mutation spectrum and quasispecies, high- and low-fidelity variants have been isolated for several RNA viruses. Here, we report the discovery of a low-fidelity RdRp variant of influenza A virus that contains a substitution at Tyr82 in PB1. Viruses containing the PB1-Y82C substitution showed growth kinetics and viral RNA synthesis levels similar to those of the wild-type virus in cell culture; however, they had significantly attenuated phenotypes in a chicken egg infection experiment. These data demonstrated that decreased RdRp fidelity attenuates influenza A virus in vivo , which is a desirable feature for the development of safer live attenuated vaccine candidates.","is_dataset_classified":null,"base_score":1.9459101490553132,"endowment":1.9459101490553132,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"31462570","pmcid":"PMC6819930","openalex_id":"https://openalex.org/W2970236921","authors":[],"funders":[{"funder_name":"MEXT | Japan Society for the Promotion of Science","grant_id":"17K09170","title":null},{"funder_name":"Japan Agency for Medical Research and Development","grant_id":"JP18lm0203008","title":null},{"funder_name":"Takeda Science Foundation","grant_id":"","title":null},{"funder_name":"Project Research Grants of Kawasaki Medical School","grant_id":"","title":null},{"funder_name":"Okayama Medical Foundation","grant_id":"","title":null}],"total_grants":5,"fwci":0.4717,"citation_percentile":0.67068464,"influential_citations":0,"citation_trend":[{"year":2021,"count":2},{"year":2022,"count":1},{"year":2023,"count":1},{"year":2025,"count":1},{"year":2026,"count":1}],"oa_status":"bronze","license":null,"oa_locations":[{"url":"https://jvi.asm.org/content/jvi/93/22/e00834-19.full.pdf","host_type":"journal"},{"url":"https://jvi.asm.org/content/jvi/93/22/e00834-19.full.pdf","host_type":"publisher"},{"url":"https://doi.org/10.1128/jvi.00834-19","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/31462570","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/6819930","host_type":"repository"}],"fields_of_study":["Influenza Virus Research Studies","Bacteriophages and microbial interactions","RNA and protein synthesis mechanisms"],"mesh_terms":["Amino Acid Sequence","Animals","Dogs","Humans","Models, Molecular","Mutation","Influenza A virus","Phenotype","RNA-Dependent RNA Polymerase","RNA, Viral","Viral Proteins","Virus Replication","Amino Acid Substitution","Polymorphism, Single Nucleotide","HEK293 Cells","Madin Darby Canine Kidney Cells"],"keywords":["Viral quasispecies","Biology","Virology","Virus","Polymerase","Influenza A virus","RNA polymerase","Mutation","RNA virus","Mutation rate","Viral evolution","RNA-dependent RNA polymerase","RNA","Mutagenesis","Genetics","Gene","Hepatitis C virus","RNA polymerases","Influenza","Fidelity","Mutator"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"bioproject"},{"name":"pdb"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-27T16:40:14.330339Z","pmid":null,"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":[]}