{"doi":"10.4049/immunohorizons.2300026","title":"Human Metapneumovirus Reinfection in Aged Mice Recapitulates Increased Disease Severity in Elderly Humans Infected with Human Metapneumovirus","abstract":"Human metapneumovirus (HMPV) is a leading cause of respiratory infection in adults >65 y. Nearly all children worldwide are seropositive for HMPV by age 5 y, but reinfections occur throughout life, and there is no licensed vaccine. Recurrent HMPV infection is mild and self-resolving in immunocompetent individuals. However, elderly individuals develop severe respiratory disease on HMPV reinfection that leads to a high risk for morbidity and mortality. In this study, we developed a mouse model to mirror HMPV reinfection in elderly humans. C57BL/6J mice were infected with HMPV at 6-7 wk old, aged in-house, and rechallenged with high-dose virus at 70 wk. Aged rechallenged mice had profound weight loss similar to primary infected mice, increased lung histopathology, and accumulated cytotoxic CD8+CD44+CD62L-CD69+CD103+ memory cells despite having undetectable lung virus titer. When aged mice 14 mo postinfection (p.i.) or young mice 5 wk p.i. were restimulated with HMPV cognate Ag to mimic epitope vaccination, aged mice had an impaired CD8+ memory response. Convalescent serum transfer from young naive or 5 wk p.i. mice into aged mice on day of infection did not protect. Aged mice vaccinated with UV-inactivated HMPV also exhibited diminished protection and poor CD8+ memory response compared with young mice. These results suggest aged individuals with HMPV reinfection have a dysregulated CD8+ memory T cell response that fails to protect and exacerbates disease. Moreover, aged mice exhibited a poor memory response to either epitope peptide or UV-inactivated vaccination, suggesting that aged CD8+ T cell dysfunction presents a barrier to effective vaccination strategies.","journal":"ImmunoHorizons","year":2023,"id":342750,"datarank":0.45473600816856197,"base_score":2.70805020110221,"endowment":2.70805020110221,"self_citation_contribution":0.40620753016533157,"citation_network_contribution":0.04852847800323042,"self_endowment_contribution":0.40620753016533157,"citer_contribution":0.04852847800323042,"corpus_percentile":null,"corpus_rank":null,"citation_count":14,"citer_count":8,"citers_with_citation_signal":5,"citers_with_endowment":5,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9577,"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":780746,"name":"Taylor Eddens","orcid":"0000-0003-2969-3624","position":1,"is_corresponding":false},{"id":104143,"name":"Yu Zhang","orcid":"0000-0002-6904-0372","position":2,"is_corresponding":false},{"id":315201,"name":"Tim D. Oury","orcid":"0000-0002-4253-3214","position":3,"is_corresponding":false},{"id":218428,"name":"Anita K. McElroy","orcid":"0000-0001-6764-7536","position":4,"is_corresponding":false},{"id":236968,"name":"John V. Williams","orcid":"0000-0001-8377-5175","position":5,"is_corresponding":false},{"id":657355,"name":"Olivia B. Parks","orcid":"0000-0003-1131-9407","position":0,"is_corresponding":true}],"reference_count":49,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:11:17.288563Z","pmid":"37261717","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":[]}