{"doi":"10.1101/2024.12.22.629980","title":"The CD4 T cell-independent IgG response during persistent virus infection favors emergence of neutralization-escape variants","abstract":"How changes in the quality of anti-viral antibody (Ab) responses due to pre-existing or acquired CD4 T cell insufficiency affect virus evolution during persistent infection are unknown. Using mouse polyomavirus (MuPyV), we found that CD4 T cell depletion before infection results in short-lived plasma cells secreting low-avidity antiviral IgG with limited BCR diversity and weak virus-neutralizing ability. CD4 T cell deficiency during persistent infection incurs a shift from a T-dependent (TD) to T-independent (TI) Ab response, resembling the pre-existing TI Ab response. CD4 T cell loss before infection or during persistent infection is conducive for emergence of Ab-escape variants. Cryo-EM reconstruction of complexes of MuPyV virions with polyclonal IgG directly from infected mice with pre-existing or acquired CD4 T cell deficiency enabled visualization of shortfalls in TI IgG binding. By debilitating the antiviral IgG response, CD4 T cell deficiency sets the stage for outgrowth of variant viruses resistant to neutralization.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":486499,"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":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9585,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":913614,"name":"Matthew D. Lauver","orcid":"0000-0002-7001-9730","position":1,"is_corresponding":false},{"id":1330347,"name":"Kalynn M Alexander","orcid":"0000-0001-8749-5744","position":2,"is_corresponding":false},{"id":994947,"name":"Ge Jin","orcid":"0000-0001-9639-1330","position":3,"is_corresponding":false},{"id":398243,"name":"Kitt Paraiso","orcid":"0000-0002-6489-810X","position":4,"is_corresponding":false},{"id":1086417,"name":"Alyssa Ochetto","orcid":"0000-0001-8917-0978","position":5,"is_corresponding":false},{"id":1299497,"name":"Sonal Garg","orcid":"0000-0002-0004-7939","position":6,"is_corresponding":false},{"id":463163,"name":"Daniel J. Goetschius","orcid":"0000-0002-6052-7141","position":7,"is_corresponding":false},{"id":463166,"name":"Susan Hafenstein","orcid":"0000-0003-2609-4036","position":8,"is_corresponding":false},{"id":318449,"name":"Joseph Che‐Yen Wang","orcid":"0000-0001-6580-3531","position":9,"is_corresponding":false},{"id":913618,"name":"Aron E. Lukacher","orcid":"0000-0002-7969-2841","position":10,"is_corresponding":false},{"id":913616,"name":"Katelyn N. Ayers","orcid":"0000-0001-6156-8685","position":0,"is_corresponding":true}],"reference_count":55,"raw_metadata":null,"created_at":"2026-07-19T02:08:01.404471Z","pmid":"39763786","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":[]}