{"doi":"10.1093/infdis/jiad424","title":"Upregulation of the NKG2D Ligand ULBP2 by JC Polyomavirus Infection Promotes Immune Recognition by Natural Killer Cells","abstract":"BACKGROUND: JC polyomavirus (JCPyV) causes progressive multifocal leukoencephalopathy (PML), a potentially fatal complication of severe immune suppression with no effective treatment. Natural killer (NK) cells play critical roles in defense against viral infections; however, NK-cell response to JCPyV infection remains unexplored. METHODS: NK- and T-cell responses against the JCPyV VP1 were compared using intracellular cytokine staining upon stimulation with peptide pools. A novel flow cytometry-based assay was developed to determine NK-cell killing efficiency of JCPyV-infected astrocyte-derived SVG-A cells. Blocking antibodies were used to evaluate the contribution of NK-cell receptors in immune recognition of JCPyV-infected cells. RESULTS: In about 40% of healthy donors, we detected robust CD107a upregulation and IFN-γ production by NK cells, extending beyond T-cell responses. Next, using the NK-cell-mediated killing assay, we showed that coculture of NK cells and JCPyV-infected SVG-A cells leads to a 60% reduction in infection, on average. JCPyV-infected cells had enhanced expression of ULBP2-a ligand for the activating NK-cell receptor NKG2D, and addition of NKG2D blocking antibodies decreased NK-cell degranulation. CONCLUSIONS: NKG2D-mediated activation of NK cells plays a key role in controlling JCPyV replication and may be a promising immunotherapeutic target to boost NK-cell anti-JCPyV activity.","journal":"The Journal of Infectious Diseases","year":2023,"id":382521,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9644,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":528891,"name":"Jenny Ahn","orcid":"0009-0000-3912-7162","position":1,"is_corresponding":false},{"id":1149030,"name":"Sarah Chen","orcid":"0000-0001-8966-7984","position":2,"is_corresponding":false},{"id":1025332,"name":"Taylor Yoder","orcid":"0009-0002-6077-5206","position":3,"is_corresponding":false},{"id":1149513,"name":"Kayitare Eunice Gikundiro","orcid":null,"position":4,"is_corresponding":false},{"id":256311,"name":"Esther Lee","orcid":"0000-0002-5820-6111","position":5,"is_corresponding":false},{"id":1149031,"name":"Simon B. Gressens","orcid":"0000-0002-4993-6956","position":6,"is_corresponding":false},{"id":435422,"name":"Kyle Kroll","orcid":"0000-0002-9237-9497","position":7,"is_corresponding":false},{"id":1149514,"name":"Melissa Craemer","orcid":null,"position":8,"is_corresponding":false},{"id":1149032,"name":"G. Campbell Kaynor","orcid":"0000-0002-7158-3405","position":9,"is_corresponding":false},{"id":107600,"name":"Michelle A. Lifton","orcid":"0000-0003-0279-2198","position":10,"is_corresponding":false},{"id":345903,"name":"Chen Sabrina Tan","orcid":"0000-0001-7604-0824","position":11,"is_corresponding":false},{"id":778384,"name":"Stéphanie Jost","orcid":"0000-0003-2100-3262","position":0,"is_corresponding":true}],"reference_count":51,"raw_metadata":null,"created_at":"2026-07-19T01:17:20.969491Z","pmid":"37774496","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":[]}