{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T17:38:28Z","timestamp":1790271508679,"version":"4.1.0"},"reference-count":67,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2025,8,12]],"date-time":"2025-08-12T00:00:00Z","timestamp":1754956800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010446","name":"Institute for Basic Science","doi-asserted-by":"publisher","award":["IBS-R801-D1"],"award-info":[{"award-number":["IBS-R801-D1"]}],"id":[{"id":"10.13039\/501100010446","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"national research foundation of korea","doi-asserted-by":"crossref","award":["NRF-2020R1A2C3008339"],"award-info":[{"award-number":["NRF-2020R1A2C3008339"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National institute of healt","award":["AI171201"],"award-info":[{"award-number":["AI171201"]}]},{"name":"National institute of Health","award":["AI152190"],"award-info":[{"award-number":["AI152190"]}]},{"name":"The Korea-US collaborative Research Fun","award":["RS-2024-00467046"],"award-info":[{"award-number":["RS-2024-00467046"]}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    Aging significantly influences host immune responses to viral infections, including Severe Fever with Thrombocytopenia Syndrome Virus (SFTSV), which is associated with high mortality in elderly patients. Despite its high fatality rate and pandemic potential, effective therapies remain unavailable, and the age-dependent mechanisms underlying SFTSV pathogenesis are not fully understood. To address this gap, we employed a ferret model (an immunocompetent animal model that mimics human SFTSV infections) and performed multi-tissue single-cell RNA sequencing and histopathological analyses. Our results reveal that, upon SFTSV infection, aged ferrets experience extensive decrease of critical immune cells (particularly B and T cells) due to infection-induced cell death and excessive hemophagocytosis in hematopoietic organs, whereas young-adult ferrets rapidly clear the virus with minimal lymphocyte changes. Notably, aged ferrets display marked immune dysregulation, characterized by non-specific activation of\n                    <jats:italic>\n                      <jats:italic>T-bet<\/jats:italic>\n                    <\/jats:italic>\n                    \u2009\u207a\u2009age-associated memory B cells (\n                    <jats:italic>\n                      <jats:italic>T-bet<\/jats:italic>\n                    <\/jats:italic>\n                    <jats:sup>+<\/jats:sup>\n                    ABCs) and the proliferation of defective plasmablasts (\n                    <jats:italic>MKI67<\/jats:italic>\n                    \u2009\u207a\u2009PB1), which serve as major viral reservoirs and drive systemic viral dissemination. Comparative analysis further demonstrated that the\n                    <jats:italic>MKI67<\/jats:italic>\n                    \u2009\u207a\u2009PB1 subset dominates SFTSV\u207a cells in both aged ferrets and human fatal cases, exhibiting the highest per-cell viral UMI counts. Moreover, monocytes and macrophages in aged ferrets exhibit heightened inflammatory gene expression, contributing to the hyper-inflammatory state observed during infection. Collectively, these insights underscore the critical role of dysregulated memory B cell responses and hyper-inflammation in age-dependent SFTSV pathogenesis, highlighting potential targets for interventions in elderly populations.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1013402","type":"journal-article","created":{"date-parts":[[2025,8,12]],"date-time":"2025-08-12T17:24:43Z","timestamp":1755019483000},"page":"e1013402","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":7,"title":["Age-associated immune dysregulation and B cell dysfunction drive severe outcomes in SFTSV infection"],"prefix":"10.1371","volume":"21","author":[{"given":"Eun-Ha","family":"Kim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ho Bin","family":"Jang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Se-Mi","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongbin","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young-Il","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung-Gyu","family":"Jang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suhee","family":"Hwang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Woo-Hyun","family":"Kwon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isaac","family":"Choi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaemoo","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hee-Dong","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyunjoon","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark Anthony B.","family":"Casel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min-Suk","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae U.","family":"Jung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0872-0147","authenticated-orcid":true,"given":"Young Ki","family":"Choi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,8,12]]},"reference":[{"issue":"9","key":"ppat.1013402.ref001","doi-asserted-by":"crossref","DOI":"10.3201\/eid2409.171427","article-title":"World Health Organization Methodology to Prioritize Emerging Infectious Diseases in Need of Research and Development","volume":"24","author":"MS Mehand","year":"2018","journal-title":"Emerg Infect 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Sun","year":"2022","journal-title":"Front Microbiol"},{"issue":"1","key":"ppat.1013402.ref033","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.cvex.2009.12.002","article-title":"The senior ferret (Mustela putorius furo)","volume":"13","author":"SM Hoppes","year":"2010","journal-title":"Vet Clin North Am Exot Anim Pract"},{"key":"ppat.1013402.ref034","article-title":"Human Ageing Genomic Resources: updates on key databases in ageing research","volume":"52","author":"JP de Magalh\u00e3es","year":"2024","journal-title":"Nucleic Acids Res"},{"issue":"12","key":"ppat.1013402.ref035","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1038\/ni1201-1103","article-title":"Plasma cells: finding new light at the end of B cell development","volume":"2","author":"KL Calame","year":"2001","journal-title":"Nat Immunol"},{"key":"ppat.1013402.ref036","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1146\/annurev-immunol-092419-031130","article-title":"Age-Associated B 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