{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T03:53:03Z","timestamp":1793764383218,"version":"4.6.1"},"reference-count":28,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T00:00:00Z","timestamp":1753315200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Key Project of Yunnan Province","award":["202202AA100001"],"award-info":[{"award-number":["202202AA100001"]}]},{"name":"Key Project of Yunnan Province","award":["202301AS070066"],"award-info":[{"award-number":["202301AS070066"]}]},{"name":"Yunnan Applied Basic Research Projects","award":["202202AA100001"],"award-info":[{"award-number":["202202AA100001"]}]},{"name":"Yunnan Applied Basic Research Projects","award":["202301AS070066"],"award-info":[{"award-number":["202301AS070066"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Coxsackievirus B3 (CV-B3) infection causes inflammatory conditions such as viral myocarditis and meningitis, and incidence rates are rising annually. While children are more likely to be affected by severe manifestations, the molecular basis of this age-dependent susceptibility is poorly understood. In this study, we used young Balb\/c mice at three developmental stages (7-, 14-, and 30-day-old mice) to investigate CV-B3 pathogenesis. Our findings revealed that 7-day-old mice exhibited substantial infection susceptibility and pathological severity compared to older mice. Critically, an age-dependent analysis showed a progressive decline in the expression of CV-B3-binding Coxsackievirus and Adenovirus Receptor (CAR) splice variants (CAR1 and CAR2) at both the transcriptional and translational levels as the mice matured from 7 to 30 days. These receptor isoforms demonstrated a direct correlation with viral replication efficiency in younger hosts. Concurrently, aging was associated with a rise in non-binding CAR variants (CAR3 and CAR4). During CV-B3 infection, the abundance of CAR1\/CAR2 in young mice facilitated accelerated viral proliferation, coupled with the hyperactivation of the NLRP3 inflammasome and the expansion of IL-17-producing \u03b3\u03b4T cells (\u03b3\u03b4T17 cells). This cascade triggered excessive production of proinflammatory cytokines (IL-1\u03b2, IL-18, and IL-17), culminating in pronounced inflammatory infiltrates within cardiac and cerebral tissues. These findings establish NLRP3 inflammasome dysregulation as a critical determinant of CV-B3-induced tissue damage and provide novel insights into the heightened susceptibility to CV-B infection during early life and its associated severe disease rates.<\/jats:p>","DOI":"10.3390\/ijms26157163","type":"journal-article","created":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T15:19:22Z","timestamp":1753370362000},"page":"7163","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The Expression Pattern of the Splice Variants of Coxsackievirus and Adenovirus Receptor Impacts CV-B3-Induced Encephalitis and Myocarditis in Neonatal Mice"],"prefix":"10.3390","volume":"26","author":[{"given":"Xinglong","family":"Zhang","sequence":"first","affiliation":[{"name":"Institute of Medical Biology, Chinese Academy of Medicine Sciences, Peking Union Medical College, Kunming 650031, China"},{"name":"Key Laboratory of Systemic Innovative Research on Virus Vaccine, Institute of Medical Biology, Chinese Academy of Medical Sciences, Peking Union Medical College, Kunming 650118, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Medical Biology, Chinese Academy of Medicine Sciences, Peking Union Medical College, Kunming 650031, China"},{"name":"Key Laboratory of Systemic Innovative Research on Virus Vaccine, Institute of Medical Biology, Chinese Academy of Medical Sciences, Peking Union Medical College, Kunming 650118, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Medical Biology, Chinese Academy of Medicine Sciences, Peking Union Medical College, Kunming 650031, China"},{"name":"Key Laboratory of Systemic Innovative Research on Virus Vaccine, Institute of Medical Biology, Chinese Academy of Medical 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjing","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Medical Biology, Chinese Academy of Medicine Sciences, Peking Union Medical College, Kunming 650031, China"},{"name":"Key Laboratory of Systemic Innovative Research on Virus Vaccine, Institute of Medical Biology, Chinese Academy of Medical Sciences, Peking Union Medical College, Kunming 650118, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Liao","sequence":"additional","affiliation":[{"name":"Institute of Medical Biology, Chinese Academy of Medicine Sciences, Peking Union Medical College, Kunming 650031, China"},{"name":"Key Laboratory of Systemic Innovative Research on Virus Vaccine, Institute of Medical Biology, Chinese Academy of Medical Sciences, Peking Union Medical College, Kunming 650118, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Yu","sequence":"additional","affiliation":[{"name":"Institute of Medical Biology, Chinese Academy of Medicine Sciences, Peking Union Medical College, Kunming 650031, China"},{"name":"Key Laboratory of Systemic Innovative Research on Virus Vaccine, Institute of Medical Biology, Chinese Academy of Medical Sciences, Peking Union Medical College, Kunming 650118, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3527-3522","authenticated-orcid":false,"given":"Dandan","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Medical Biology, Chinese Academy of Medicine Sciences, Peking Union Medical College, Kunming 650031, China"},{"name":"Key Laboratory of Systemic Innovative Research on Virus Vaccine, Institute of Medical Biology, Chinese Academy of Medical Sciences, Peking Union Medical College, Kunming 650118, 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Sciences, Peking Union Medical College, Kunming 650118, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zihan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Medical Biology, Chinese Academy of Medicine Sciences, Peking Union Medical College, Kunming 650031, China"},{"name":"Key Laboratory of Systemic Innovative Research on Virus Vaccine, Institute of Medical Biology, Chinese Academy of Medical Sciences, Peking Union Medical College, Kunming 650118, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haijing","family":"Shi","sequence":"additional","affiliation":[{"name":"Institute of Medical Biology, Chinese Academy of Medicine Sciences, Peking Union Medical College, Kunming 650031, China"},{"name":"Key Laboratory of Systemic Innovative Research on Virus Vaccine, Institute of Medical Biology, Chinese Academy of Medical Sciences, Peking Union Medical College, Kunming 650118, 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