{"doi":"10.7554/elife.83030","title":"T cell deficiency precipitates antibody evasion and emergence of neurovirulent polyomavirus","abstract":"JC polyomavirus (JCPyV) causes progressive multifocal leukoencephalopathy (PML), a life-threatening brain disease in immunocompromised patients. Inherited and acquired T cell deficiencies are associated with PML. The incidence of PML is increasing with the introduction of new immunomodulatory agents, several of which target T cells or B cells. PML patients often carry mutations in the JCPyV VP1 capsid protein, which confer resistance to neutralizing VP1 antibodies (Ab). Polyomaviruses (PyV) are tightly species-specific; the absence of tractable animal models has handicapped understanding PyV pathogenesis. Using mouse polyomavirus (MuPyV), we found that T cell deficiency during persistent infection, in the setting of monospecific VP1 Ab, was required for outgrowth of VP1 Ab-escape viral variants. CD4 T cells were primarily responsible for limiting polyomavirus infection in the kidney, a major reservoir of persistent infection by both JCPyV and MuPyV, and checking emergence of these mutant viruses. T cells also provided a second line of defense by controlling the outgrowth of VP1 mutant viruses that evaded Ab neutralization. A virus with two capsid mutations, one conferring Ab-escape yet impaired infectivity and a second compensatory mutation, yielded a highly neurovirulent variant. These findings link T cell deficiency and evolution of Ab-escape polyomavirus VP1 variants with neuropathogenicity.","journal":"eLife","year":2022,"id":260366,"datarank":0.5154227237169261,"base_score":2.833213344056216,"endowment":2.833213344056216,"self_citation_contribution":0.42498200160843247,"citation_network_contribution":0.0904407221084936,"self_endowment_contribution":0.42498200160843247,"citer_contribution":0.0904407221084936,"corpus_percentile":null,"corpus_rank":null,"citation_count":16,"citer_count":8,"citers_with_citation_signal":6,"citers_with_endowment":6,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9643,"is_data_producer":true,"deposit_databanks":{"Dryad":["10.5061/dryad.prr4xgxqj"]},"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":913615,"name":"Ge Jin","orcid":"0000-0002-9427-4023","position":1,"is_corresponding":false},{"id":913616,"name":"Katelyn N. Ayers","orcid":"0000-0001-6156-8685","position":2,"is_corresponding":false},{"id":913617,"name":"Sarah N. Carey","orcid":"0000-0002-8801-5420","position":3,"is_corresponding":false},{"id":914079,"name":"Charles S Specht","orcid":null,"position":4,"is_corresponding":false},{"id":758541,"name":"Catherine Abendroth","orcid":"0000-0002-1036-3652","position":5,"is_corresponding":false},{"id":913618,"name":"Aron E. Lukacher","orcid":"0000-0002-7969-2841","position":6,"is_corresponding":false},{"id":913614,"name":"Matthew D. Lauver","orcid":"0000-0002-7001-9730","position":0,"is_corresponding":true}],"reference_count":85,"raw_metadata":null,"created_at":"2026-07-19T00:26:03.189798Z","pmid":"36341713","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":[]}