{"doi":"10.1128/jvi.02743-06","title":"Epstein-Barr Virus Inhibits Kaposi's Sarcoma-Associated Herpesvirus Lytic Replication in Primary Effusion Lymphomas","abstract":"<jats:title>ABSTRACT</jats:title>\n          <jats:p>The majority of AIDS-associated primary effusion lymphomas (PEL) are latently infected with both Kaposi's sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV). PELs harboring two viruses have higher oncogenic potential, suggesting functional interactions between EBV and KSHV. The KSHV replication and transcription activator (K-RTA) is necessary and sufficient for induction of KSHV lytic replication. EBV latent membrane protein 1 (LMP-1) is essential for EBV transformation and establishment of latency in vitro. We show EBV inhibits chemically induced KSHV lytic replication, in part because of a regulatory loop in which K-RTA induces EBV LMP-1 and LMP-1 in turn inhibits K-RTA expression and furthermore the lytic gene expression of KSHV. Suppression of LMP-1 expression in dually infected PEL cells enhances the expression of K-RTA and lytic replication of KSHV upon chemical induction. Because LMP-1 is known to inhibit EBV lytic replication, KSHV-mediated induction of LMP-1 would potentiate EBV latency. Moreover, KSHV infection of EBV latency cells induces LMP-1, and K-RTA is involved in the induction. Both LMP-1 and K-RTA are expressed during primary infection by EBV of KSHV latency cells. Our findings provide evidence that an interaction between EBV and KSHV at molecular levels promotes the maintenance and possibly establishment of viral latency, which may contribute to pathogenesis of PELs.</jats:p>","journal":"Journal of Virology","year":2007,"id":601583,"datarank":0.586803450814222,"base_score":3.912023005428146,"endowment":3.912023005428146,"self_citation_contribution":0.586803450814222,"citation_network_contribution":0.0,"self_endowment_contribution":0.586803450814222,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":49,"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":1542559,"name":"Tricia Coleman","orcid":null,"position":1,"is_corresponding":false},{"id":106134,"name":"Jun Zhang","orcid":"0000-0002-1289-0624","position":2,"is_corresponding":false},{"id":1542560,"name":"Ashley Fagot","orcid":null,"position":3,"is_corresponding":false},{"id":1542561,"name":"Catherine Kotalik","orcid":null,"position":4,"is_corresponding":false},{"id":1542562,"name":"Lingjun Zhao","orcid":null,"position":5,"is_corresponding":false},{"id":1542563,"name":"Pankaj Trivedi","orcid":null,"position":6,"is_corresponding":false},{"id":400695,"name":"Clinton Jones","orcid":"0000-0002-6656-4971","position":7,"is_corresponding":false},{"id":478961,"name":"Luwen Zhang","orcid":"0000-0002-8876-3947","position":8,"is_corresponding":false},{"id":52639,"name":"Dongsheng Xu","orcid":"0000-0003-1646-905X","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Epstein-Barr Virus Inhibits Kaposi's Sarcoma-Associated Herpesvirus Lytic Replication in Primary Effusion Lymphomas","abstract":"<jats:title>ABSTRACT</jats:title>\n          <jats:p>The majority of AIDS-associated primary effusion lymphomas (PEL) are latently infected with both Kaposi's sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV). PELs harboring two viruses have higher oncogenic potential, suggesting functional interactions between EBV and KSHV. The KSHV replication and transcription activator (K-RTA) is necessary and sufficient for induction of KSHV lytic replication. EBV latent membrane protein 1 (LMP-1) is essential for EBV transformation and establishment of latency in vitro. We show EBV inhibits chemically induced KSHV lytic replication, in part because of a regulatory loop in which K-RTA induces EBV LMP-1 and LMP-1 in turn inhibits K-RTA expression and furthermore the lytic gene expression of KSHV. Suppression of LMP-1 expression in dually infected PEL cells enhances the expression of K-RTA and lytic replication of KSHV upon chemical induction. Because LMP-1 is known to inhibit EBV lytic replication, KSHV-mediated induction of LMP-1 would potentiate EBV latency. Moreover, KSHV infection of EBV latency cells induces LMP-1, and K-RTA is involved in the induction. Both LMP-1 and K-RTA are expressed during primary infection by EBV of KSHV latency cells. Our findings provide evidence that an interaction between EBV and KSHV at molecular levels promotes the maintenance and possibly establishment of viral latency, which may contribute to pathogenesis of PELs.</jats:p>","is_dataset_classified":null,"base_score":3.912023005428146,"endowment":3.912023005428146,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"17376914","pmcid":"PMC1900272","openalex_id":"https://openalex.org/W2158986449","authors":[],"funders":[{"funder_name":"NCI NIH HHS","grant_id":"R01CA108951","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"R21 AI059132","title":null},{"funder_name":"NCRR NIH HHS","grant_id":"P20RR15635","title":null},{"funder_name":"NCRR NIH HHS","grant_id":"P20 RR015635","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"U54 AI057160","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"R21AI59132","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"T32 AI060547","title":null}],"total_grants":7,"fwci":1.7951,"citation_percentile":0.85370693,"influential_citations":0,"citation_trend":[{"year":2012,"count":3},{"year":2013,"count":4},{"year":2014,"count":5},{"year":2015,"count":2},{"year":2016,"count":1},{"year":2017,"count":2},{"year":2018,"count":5},{"year":2019,"count":3},{"year":2020,"count":1},{"year":2021,"count":1},{"year":2022,"count":2},{"year":2023,"count":4},{"year":2025,"count":1}],"oa_status":"green","license":"https://journals.asm.org/non-commercial-tdm-license","oa_locations":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/1900272","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/1900272","host_type":"repository"},{"url":"https://journals.asm.org/doi/pdf/10.1128/JVI.02743-06","host_type":"publisher"},{"url":"https://doi.org/10.1128/jvi.02743-06","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/17376914","host_type":"repository"},{"url":"https://digitalcommons.unl.edu/virologypub/19","host_type":"repository"},{"url":"http://hdl.handle.net/11573/125595","host_type":"repository"}],"fields_of_study":["Viral-associated cancers and disorders","Cytomegalovirus and herpesvirus research","Lymphoma Diagnosis and Treatment","Amino Acid Sequence","Cell Line","Cell Line, Tumor","Herpesvirus 4, Human","Herpesvirus 8, Human","Humans","Lymphoma, AIDS-Related","Molecular Sequence Data","Pleural Effusion, Malignant","Virus Replication"],"mesh_terms":["Amino Acid Sequence","Cell Line","Herpesvirus 4, Human","Humans","Molecular Sequence Data","Virus Replication","Pleural Effusion, Malignant","Lymphoma, AIDS-Related","Herpesvirus 8, Human","Cell Line, Tumor"],"keywords":["Lytic cycle","Primary effusion lymphoma","Biology","Kaposi's sarcoma-associated herpesvirus","Virology","Gammaherpesvirinae","Virus latency","Epstein–Barr virus","Viral replication","Virus","Herpesviridae","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":"2026-07-29T16:47:35.046516Z","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":[]}