{"doi":"10.1101/2025.06.24.661167","title":"CMV-specific clonal expansion of Th1, GZMK⁺ CD8⁺, and TEMRA T cells revealed by human PBMC single cell profiling","abstract":"Abstract Cytomegalovirus (CMV) is a common herpesvirus that establishes lifelong latency and becomes increasingly prevalent with age. We systematically characterized CMV-associated immune remodeling by analyzing six human cohorts (two newly built) using single-cell RNA sequencing, T cell receptor (TCR) sequencing, and flow cytometry. Beyond the well-known expansion of CD4⁺/CD8⁺ TEMRA, adaptive NK, and γδ T cells, CMV(+) adults exhibited increased frequencies of GZMK⁺ CD8⁺ T cells and atypical B cells, alongside a reduction of CD56 dim NK cells. Longitudinal profiling of an individual who seroconverted revealed rapid CMV-driven shifts in circulating immune cell frequencies. Single-cell TCR data analyzed using a large database of CMV-associated clones combined with predictive modelling (CMVerify), identified novel CMV-specific clonal expansions reproduced across two independent cohorts. In the CD8⁺ lineage, CMV-specific clones were enriched in GZMK⁺ CD8⁺ and CD8⁺ TEMRA cells, while in the CD4⁺ lineage, Th1 cells showed clonal expansion alongside CD4⁺ TEMRA cells. This integrative study revealed how latent CMV alters the cellular and clonal landscape, defining GZMK⁺ CD8⁺ and Th1 cells as newly recognized elements of response to CMV in humans.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":558344,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9456,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1458783,"name":"Luke Trinity","orcid":"0000-0002-1578-7964","position":1,"is_corresponding":false},{"id":253997,"name":"Chris P. Verschoor","orcid":"0000-0001-6190-2655","position":2,"is_corresponding":false},{"id":225890,"name":"Djamel Nehar-Belaid","orcid":"0000-0001-6002-5021","position":3,"is_corresponding":false},{"id":229305,"name":"Radu Marcheş","orcid":null,"position":4,"is_corresponding":false},{"id":1173796,"name":"Giray Naim Eryilmaz","orcid":null,"position":5,"is_corresponding":false},{"id":728160,"name":"Avinash S. Mahajan","orcid":"0000-0003-3450-0305","position":6,"is_corresponding":false},{"id":1459220,"name":"Sathya Baarathi","orcid":null,"position":7,"is_corresponding":false},{"id":984123,"name":"Asa Thibodeau","orcid":"0000-0003-2421-4225","position":8,"is_corresponding":false},{"id":703539,"name":"Émilie Picard","orcid":"0000-0002-2689-0510","position":9,"is_corresponding":false},{"id":230632,"name":"Chia‐Ling Kuo","orcid":"0000-0003-4452-2380","position":10,"is_corresponding":false},{"id":79792,"name":"Kenneth E. Schmader","orcid":"0000-0001-5036-2155","position":11,"is_corresponding":false},{"id":373358,"name":"Cathleen Colón‐Emeric","orcid":"0000-0001-7681-8624","position":12,"is_corresponding":false},{"id":79787,"name":"Heather E. Whitson","orcid":"0000-0002-8417-4846","position":13,"is_corresponding":false},{"id":267158,"name":"Silke Paust","orcid":"0000-0002-0526-3999","position":14,"is_corresponding":false},{"id":124165,"name":"Adolfo García-Sastre","orcid":null,"position":15,"is_corresponding":false},{"id":357047,"name":"Gur Yaari","orcid":"0000-0001-9311-9884","position":16,"is_corresponding":false},{"id":55820,"name":"Jacques Banchereau","orcid":"0000-0003-3535-7221","position":17,"is_corresponding":false},{"id":225893,"name":"George A. Kuchel","orcid":"0000-0001-8387-7040","position":18,"is_corresponding":false},{"id":42663,"name":"Duygu Ucar","orcid":"0000-0002-9772-3066","position":19,"is_corresponding":false},{"id":630310,"name":"Titas Grabauskas","orcid":"0000-0002-3512-9862","position":0,"is_corresponding":true}],"reference_count":60,"raw_metadata":null,"created_at":"2026-07-19T02:55:25.969263Z","pmid":"40666903","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":[]}