{"doi":"10.1128/jvi.00923-10","title":"Cellular MicroRNAs 200b and 429 Regulate the Epstein-Barr Virus Switch between Latency and Lytic Replication","abstract":"<jats:title>ABSTRACT</jats:title>\n          <jats:p>\n            We previously showed that the cellular proteins ZEB1 and ZEB2/SIP1 both play key roles in regulating the latent-lytic switch of Epstein-Barr Virus (EBV) by repressing\n            <jats:italic>BZLF1</jats:italic>\n            gene expression. We investigated here the effects of cellular microRNA (miRNA) 200 (miR200) family members on the EBV infection status of cells. We show that miR200b and miR429, but not miR200a, can induce EBV-positive cells into lytic replication by downregulating expression of ZEB1 and ZEB2, leading to production of infectious virus. The levels of miR200 family members in EBV-infected cells strongly negatively correlated with the levels of the ZEBs (e.g., −0.89 [\n            <jats:italic>P</jats:italic>\n            &lt; 0.001] for miR429 versus ZEB1) and positively correlated with the degree of EBV lytic gene expression (e.g., 0.73 [\n            <jats:italic>P</jats:italic>\n            &lt; 0.01] for miR429 versus BZLF1). The addition of either miR200b or miR429 to EBV-positive cells led to EBV lytic reactivation in a ZEB-dependent manner; inhibition of these miRNAs led to decreased EBV lytic gene expression. The degree of latent infection by an EBV mutant defective in the primary ZEB-binding site of the EBV BZLF1 promoter was not affected by the addition of these miRNAs. Furthermore, EBV infection of primary blood B cells led to downregulation of these miRNAs and upregulation of ZEB levels. Thus, we conclude that miRNAs 200b and 429 are key regulators via their effects on expression of ZEB1 and ZEB2 of the switch between latent and lytic infection by EBV and, therefore, potential targets for development of new lytic induction therapeutics with which to treat patients with EBV-associated malignancies.\n          </jats:p>","journal":"Journal of Virology","year":2010,"id":20374,"datarank":3.2677875831674754,"base_score":4.48863636973214,"endowment":4.48863636973214,"self_citation_contribution":0.6732954554598211,"citation_network_contribution":2.5944921277076545,"self_endowment_contribution":0.6732954554598211,"citer_contribution":2.5944921277076545,"corpus_percentile":null,"corpus_rank":null,"citation_count":88,"citer_count":82,"citers_with_citation_signal":74,"citers_with_endowment":74,"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":134884,"name":"Tawin Iempridee","orcid":null,"position":1,"is_corresponding":false},{"id":134885,"name":"Iris Xu","orcid":null,"position":2,"is_corresponding":false},{"id":134886,"name":"Janet E. Mertz","orcid":null,"position":3,"is_corresponding":false},{"id":134883,"name":"Amy L. Ellis-Connell","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":4.48863636973214,"endowment":4.48863636973214,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"20668090","pmcid":"PMC2937814","openalex_id":"https://openalex.org/W2120350608","authors":[],"funders":[{"funder_name":"NCI NIH HHS","grant_id":"T32 CA09135","title":null},{"funder_name":"NCI NIH HHS","grant_id":"P01 CA22443","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"R01 AI107034","title":null},{"funder_name":"NCI NIH HHS","grant_id":"P01 CA022443","title":null},{"funder_name":"NCI NIH HHS","grant_id":"P30 CA14520","title":null},{"funder_name":"NCI NIH HHS","grant_id":"T32 CA009135","title":null},{"funder_name":"NCI NIH HHS","grant_id":"P30 CA014520","title":null}],"total_grants":7,"fwci":3.638,"citation_percentile":0.93601835,"influential_citations":5,"citation_trend":[{"year":2012,"count":5},{"year":2013,"count":5},{"year":2014,"count":10},{"year":2015,"count":7},{"year":2016,"count":8},{"year":2017,"count":3},{"year":2018,"count":3},{"year":2019,"count":7},{"year":2020,"count":5},{"year":2021,"count":2},{"year":2022,"count":2},{"year":2023,"count":4},{"year":2024,"count":6},{"year":2025,"count":5},{"year":2026,"count":2}],"oa_status":"green","license":"https://journals.asm.org/non-commercial-tdm-license","oa_locations":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/2937814","host_type":"repository"},{"url":"https://europepmc.org/articles/pmc2937814?pdf=render","host_type":"GREEN"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/2937814","host_type":"repository"},{"url":"https://journals.asm.org/doi/pdf/10.1128/JVI.00923-10","host_type":"publisher"},{"url":"https://doi.org/10.1128/jvi.00923-10","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/20668090","host_type":"repository"}],"fields_of_study":["Viral-associated cancers and disorders","Extracellular vesicles in disease","Circular RNAs in diseases","Medicine","Biology","Base Sequence","Cell Line","DNA, Viral","Down-Regulation","Epstein-Barr Virus Infections","Genes, Viral","Herpesvirus 4, Human","Homeodomain Proteins","Host-Pathogen Interactions","Humans","MicroRNAs","Models, Biological","Promoter Regions, Genetic","Repressor Proteins","Trans-Activators","Transcription Factors","Virus Latency","Virus Replication","Zinc Finger E-box Binding Homeobox 2","Zinc Finger E-box-Binding Homeobox 1"],"mesh_terms":["Zinc Finger E-box-Binding Homeobox 1","Zinc Finger E-box Binding Homeobox 2","Base Sequence","Cell Line","DNA, Viral","Herpesvirus 4, Human","Genes, Viral","Humans","Models, Biological","Promoter Regions, Genetic","Repressor Proteins","Transcription Factors","Virus Replication","Trans-Activators","Down-Regulation","Virus Latency","Homeodomain Proteins","Epstein-Barr Virus Infections","MicroRNAs","Host-Pathogen Interactions"],"keywords":["Lytic cycle","BZLF1","Biology","Epstein–Barr virus","microRNA","Virus latency","Gammaherpesvirinae","Virus","Downregulation and upregulation","Virology","Herpesviridae","Viral replication","Gene","Genetics","Viral disease"],"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":"2026-06-04T09:13:45.563158Z","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":[]}