{"doi":"10.4049/jimmunol.2200320","title":"Novel Lymphocytic Choriomeningitis Virus Strain Sustains Abundant Exhausted Progenitor CD8 T Cells without Systemic Viremia","abstract":"Abstract Lymphocytic choriomeningitis virus (LCMV) is the prototypic arenavirus and a natural mouse pathogen. LCMV-Armstrong, an acutely resolved strain, and LCMV-clone 13, a mutant that establishes chronic infection, have provided contrasting infection models that continue to inform the fundamental biology of T cell differentiation, regulation of exhaustion, and response to checkpoint blockade. In this study, we report the isolation and characterization of LCMV-Minnesota (LCMV-MN), which was naturally transmitted to laboratory mice upon cohousing with pet shop mice and shares 80–95% amino acid homology with previously characterized LCMV strains. Infection of laboratory mice with purified LCMV-MN resulted in viral persistence that was intermediate between LCMV-Armstrong and -clone 13, with widely disseminated viral replication and viremia that was controlled within 15–30 d, unless CD4 T cells were depleted prior to infection. LCMV-MN–responding CD8+ T cells biased differentiation toward the recently described programmed death-1 (PD-1)+CXCR5+Tim-3lo stemlike CD8+ T cell population (also referred to as progenitor exhausted T cells) that effectuates responses to PD-1 blockade checkpoint inhibition, a therapy that rejuvenates responses against chronic infections and cancer. This subset resembled previously characterized PD-1+TCF1+ stemlike CD8+ T cells by transcriptional, phenotypic, and functional assays, yet was atypically abundant. LCMV-MN may provide a tool to better understand the breadth of immune responses in different settings of chronic Ag stimulation as well as the ontogeny of progenitor exhausted T cells and the regulation of responsiveness to PD-1 blockade.","journal":"The Journal of Immunology","year":2022,"id":278877,"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":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9562,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":608041,"name":"Milcah C. Scott","orcid":"0000-0003-2151-7335","position":1,"is_corresponding":false},{"id":647267,"name":"Mark Pierson","orcid":null,"position":2,"is_corresponding":false},{"id":253810,"name":"Vineet Joag","orcid":"0000-0002-0723-3347","position":3,"is_corresponding":false},{"id":266262,"name":"Sathi Wijeyesinghe","orcid":"0000-0002-8819-2654","position":4,"is_corresponding":false},{"id":506924,"name":"Matthew R. Semler","orcid":"0000-0001-7754-6392","position":5,"is_corresponding":false},{"id":256760,"name":"Clare F. Quarnstrom","orcid":null,"position":6,"is_corresponding":false},{"id":107593,"name":"Kathleen Busman‐Sahay","orcid":"0000-0002-8549-0023","position":7,"is_corresponding":false},{"id":95245,"name":"Jacob D. Estes","orcid":"0000-0002-9652-6394","position":8,"is_corresponding":false},{"id":646482,"name":"Sara E. Hamilton","orcid":"0000-0002-3768-7622","position":9,"is_corresponding":false},{"id":626117,"name":"Vaiva Vezys","orcid":"0000-0002-2520-809X","position":10,"is_corresponding":false},{"id":246460,"name":"David H. O’Connor","orcid":"0000-0003-2139-470X","position":11,"is_corresponding":false},{"id":252445,"name":"David Masopust","orcid":"0000-0002-9440-3884","position":12,"is_corresponding":false},{"id":266260,"name":"Lalit K. Beura","orcid":"0000-0002-8597-3949","position":0,"is_corresponding":true}],"reference_count":48,"raw_metadata":null,"created_at":"2026-07-19T00:28:51.322666Z","pmid":"36122933","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":[]}