{"doi":"10.1128/jvi.06840-11","title":"The Ubiquitin-Specific Protease USP7 Modulates the Replication of Kaposi's Sarcoma-Associated Herpesvirus Latent Episomal DNA","abstract":"<jats:title>ABSTRACT</jats:title>\n          <jats:p>\n            Kaposi's sarcoma herpesvirus (KSHV) belongs to the gamma-2\n            <jats:named-content content-type=\"genus-species\">Herpesviridae</jats:named-content>\n            and is associated with three neoplastic disorders: Kaposi's sarcoma (KS), primary effusion lymphoma (PEL), and multicentric Castleman's disease (MCD). The viral latency-associated nuclear antigen 1 (LANA) is expressed in all latently KSHV-infected cells and is involved in viral latent replication and maintenance of the viral genome. We show that LANA interacts with the ubiquitin-specific protease USP7 through its N-terminal TRAF (tumor necrosis factor [TNF] receptor-associated factor) domain. This interaction involves a short sequence (amino acids [aa] 971 to 986) within the C-terminal domain of LANA with strong similarities to the USP7 binding site of the Epstein-Barr virus (EBV) EBNA-1 protein. A LANA mutant with a deletion of the identified USP7 binding site showed an enhanced ability to replicate a plasmid containing the KSHV latent origin of replication but was comparable to the wild-type LANA (LANA WT) with regard to the regulation of viral and cellular promoters. Furthermore, the LANA homologues of two other gamma-2 herpesviruses, MHV68 and RRV, also recruit USP7. Our findings suggest that recruitment of USP7 to LANA could play a role in the regulation of viral latent replication. The recruitment of USP7, and its role in herpesvirus latent replication, previously described for the latent EBNA-1 protein of the gamma-1 herpesvirus (lymphocryptovirus) EBV (M. N. Holowaty et al., J. Biol. Chem. 278:29987–29994, 2003), may thereby be a conserved feature among gammaherpesvirus latent origin binding proteins.\n          </jats:p>","journal":"Journal of Virology","year":2012,"id":35124,"datarank":2.7025345445076927,"base_score":4.1588830833596715,"endowment":4.1588830833596715,"self_citation_contribution":0.6238324625039509,"citation_network_contribution":2.078702082003742,"self_endowment_contribution":0.6238324625039509,"citer_contribution":2.078702082003742,"corpus_percentile":null,"corpus_rank":null,"citation_count":63,"citer_count":61,"citers_with_citation_signal":57,"citers_with_endowment":57,"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":180532,"name":"Susann Santag","orcid":null,"position":1,"is_corresponding":false},{"id":180533,"name":"Magdalena Weidner-Glunde","orcid":null,"position":2,"is_corresponding":false},{"id":180534,"name":"Eva Gellermann","orcid":null,"position":3,"is_corresponding":false},{"id":180535,"name":"Semra Kati","orcid":null,"position":4,"is_corresponding":false},{"id":180536,"name":"Marcel Pietrek","orcid":null,"position":5,"is_corresponding":false},{"id":180537,"name":"Abel Viejo-Borbolla","orcid":null,"position":6,"is_corresponding":false},{"id":180538,"name":"Thomas F. Schulz","orcid":null,"position":7,"is_corresponding":false},{"id":180531,"name":"Wiebke Jäger","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":4.1588830833596715,"endowment":4.1588830833596715,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"22514345","pmcid":"PMC3393575","openalex_id":"https://openalex.org/W2155090438","authors":[],"funders":[],"total_grants":0,"fwci":2.7361,"citation_percentile":0.91142364,"influential_citations":3,"citation_trend":[{"year":2012,"count":2},{"year":2013,"count":8},{"year":2014,"count":3},{"year":2015,"count":5},{"year":2016,"count":5},{"year":2017,"count":6},{"year":2018,"count":5},{"year":2019,"count":10},{"year":2020,"count":1},{"year":2021,"count":3},{"year":2022,"count":3},{"year":2023,"count":2},{"year":2024,"count":1},{"year":2025,"count":8},{"year":2026,"count":1}],"oa_status":"bronze","license":"https://journals.asm.org/non-commercial-tdm-license","oa_locations":[{"url":"https://jvi.asm.org/content/jvi/86/12/6745.full.pdf","host_type":"journal"},{"url":"https://europepmc.org/articles/pmc3393575?pdf=render","host_type":"GREEN"},{"url":"https://jvi.asm.org/content/jvi/86/12/6745.full.pdf","host_type":"publisher"},{"url":"https://journals.asm.org/doi/pdf/10.1128/JVI.06840-11","host_type":"publisher"},{"url":"https://doi.org/10.1128/jvi.06840-11","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/22514345","host_type":"repository"},{"url":"http://hdl.handle.net/10261/115028","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/3393575","host_type":"repository"}],"fields_of_study":["Viral-associated cancers and disorders","Cytomegalovirus and herpesvirus research","Histiocytic Disorders and Treatments","Biology","Medicine","Antigens, Viral","Cell Line","DNA, Viral","Herpesviridae Infections","Herpesvirus 8, Human","Humans","Nuclear Proteins","Protein Binding","Ubiquitin Thiolesterase","Ubiquitin-Specific Peptidase 7","Viral Proteins","Virus Latency","Virus Replication"],"mesh_terms":["Ubiquitin-Specific Peptidase 7","Antigens, Viral","Cell Line","DNA, Viral","Herpesviridae Infections","Humans","Nuclear Proteins","Protein Binding","Viral Proteins","Virus Replication","Virus Latency","Herpesvirus 8, Human","Ubiquitin Thiolesterase"],"keywords":["Biology","Kaposi's sarcoma-associated herpesvirus","Virology","Gammaherpesvirinae","Viral replication","Primary effusion lymphoma","Virus latency","Virus","Viral protein","Molecular biology","Herpesviridae","Viral disease"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-10T01:16:26.595616Z","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":[]}