{"doi":"10.1002/jmv.23665","title":"Integrative effect of defective interfering RNA accumulation and helper virus attenuation is responsible for the persistent infection of Japanese encephalitis virus in BHK‐21 cells","abstract":"<jats:title>Abstract</jats:title><jats:sec><jats:label/><jats:p>Persistence of RNA viruses is often, but not always, associated with the production of defective interfering (DI) particles. To investigate possible roles of DI particles and helper viruses in RNA virus persistence, persistent infection with Japanese encephalitis virus (JEV) was established in baby hamster kidney (BHK‐21) cells. At the 6th and 7th serial undiluted passages of JEV on BHK‐21 cells, viral persistence was established spontaneously with DI RNA generation. Seven cell clones exhibiting persistent infection were obtained from the initial BHK‐21 cell batches exhibiting JEV persistence, and maintained for over 400 days. Most cell clones produced infectious particles (10<jats:sup>1</jats:sup>–10<jats:sup>5</jats:sup> PFU/ml) continuously, expressed viral proteins, and resisted homologous superinfection. Two helper viruses, chvBS6‐3 and chvBS7‐1, were isolated from two of the seven cell clones, and characterized to investigate their roles in JEV persistence. While chvBS6‐3 was restored to its full cytopathicity in the absence of DI RNA, chvBS7‐1 exhibited almost no cytopathicity, regardless of DI RNA co‐replication. Attenuation of chvBS7‐1 did not appear to be due to inadequate adsorption or genome replication, but due to inefficient egress of the assembled progeny virions, suggesting altered helper virus emergence during JEV persistence in BHK‐21 cells. These observations suggest that at least two mechanisms are involved in JEV persistence; a DI RNA‐dependent mechanism, where DI RNA co‐replication nullifies the helper virus's cytopathicity, or a DI RNA‐independent mechanism, where the helper virus is self‐attenuated. This study provides a useful in vitro tool for understanding the mechanisms underlying RNA virus persistent infections.<jats:bold><jats:italic>J Med. Virol. 85:1990–2000, 2013</jats:italic>.</jats:bold>© 2013 Wiley Periodicals, Inc.</jats:p></jats:sec>","journal":"Journal of Medical Virology","year":2013,"id":32152,"datarank":0.6061974869065987,"base_score":2.3978952727983707,"endowment":2.3978952727983707,"self_citation_contribution":0.3596842909197557,"citation_network_contribution":0.24651319598684296,"self_endowment_contribution":0.3596842909197557,"citer_contribution":0.24651319598684296,"corpus_percentile":null,"corpus_rank":null,"citation_count":10,"citer_count":8,"citers_with_citation_signal":7,"citers_with_endowment":7,"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":170764,"name":"Eunmi Choi","orcid":null,"position":1,"is_corresponding":false},{"id":170765,"name":"Yong Seok Jeong","orcid":null,"position":2,"is_corresponding":false},{"id":170763,"name":"Soo Young Park","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":2.3978952727983707,"endowment":2.3978952727983707,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"23861255","pmcid":null,"openalex_id":"https://openalex.org/W2142935324","authors":[],"funders":[{"funder_name":"Basic Science Research Institute of Kyung Hee University","grant_id":"20070672","title":null}],"total_grants":1,"fwci":0.6653,"citation_percentile":0.7743454,"influential_citations":0,"citation_trend":[{"year":2015,"count":2},{"year":2017,"count":1},{"year":2018,"count":1},{"year":2019,"count":1},{"year":2021,"count":1},{"year":2022,"count":1},{"year":2023,"count":1},{"year":2025,"count":1},{"year":2026,"count":1}],"oa_status":"closed","license":"http://onlinelibrary.wiley.com/termsAndConditions#vor","oa_locations":[{"url":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fjmv.23665","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/pdf/10.1002/jmv.23665","host_type":"publisher"},{"url":"https://doi.org/10.1002/jmv.23665","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/23861255","host_type":"repository"}],"fields_of_study":["Mosquito-borne diseases and control","Viral Infections and Vectors","Plant Virus Research Studies","Biology","Medicine","Animals","Cell Line","Cricetinae","Cytopathogenic Effect, Viral","Defective Viruses","Encephalitis Virus, Japanese","Helper Viruses","Serial Passage","Virus Integration","Virus Release"],"mesh_terms":["Animals","Cell Line","Cytopathogenic Effect, Viral","Defective Viruses","Encephalitis Virus, Japanese","Cricetinae","Helper Viruses","Serial Passage","Virus Integration","Virus Release"],"keywords":["Virology","RNA","Virus","Biology","Viral replication","Baby hamster kidney cell","Helper virus","Japanese encephalitis","Reversion","Superinfection","Encephalitis","Gene","Genetics","Phenotype","Japanese encephalitis virus","Persistence","Flavivirus","helper viruses","Defective Interfering Particle"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-09T10:41:49.408722Z","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":[]}