{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T22:18:14Z","timestamp":1783117094803,"version":"3.54.6"},"reference-count":27,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T00:00:00Z","timestamp":1779321600000},"content-version":"vor","delay-in-days":20,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2024YFC2309500"],"award-info":[{"award-number":["2024YFC2309500"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Anim Models and Exp Med"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The global spread of mpox continues to pose a threat to public health, with immunocompromised patients being at greater risk for severe disease. This study aimed to establish a lethal severe infection model using NPG (NOD.Cg\u2010\n                    <jats:italic>Prkdc<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>scid<\/jats:italic>\n                    <\/jats:sup>\n                    <jats:italic>Il2rg<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>tm1<\/jats:italic>\n                    <\/jats:sup>\n                    \/Vst) mice, a strain with profound immunodeficiency, to simulate severe mpox in immunocompromised patients and investigate disease progression, viral replication kinetics, tissue tropism, and immune responses. In our study, mice were inoculated with three doses of mpox virus (high: 2\u2009\u00d7\u200910\n                    <jats:sup>7<\/jats:sup>\n                    , medium: 2\u2009\u00d7\u200910\n                    <jats:sup>6<\/jats:sup>\n                    , low: 2\u2009\u00d7\u200910\n                    <jats:sup>5<\/jats:sup>\n                    TCID\n                    <jats:sub>50<\/jats:sub>\n                    [50% tissue culture infective dose]) or phosphate\u2010buffered saline as a negative control. Body weight, clinical signs, and survival were monitored. Viral loads in plasma and tissues, histopathological changes, and inflammatory responses were evaluated to systematically characterize the pathogenicity of mpox virus in severely immunodeficient mice. The results showed that NPG mice were highly susceptible to mpox virus, showing a clear dose\u2010dependent response. The high\u2010dose group exhibited 100% lethality, and the medium\u2010dose group had a 50% survival rate, whereas the low\u2010dose and control groups survived throughout the study. Plasma and tissue viral loads, as well as histopathological severity, followed a dose\u2010dependent pattern. Viremia remained persistently high, and animals that died at different time points exhibited uniformly high viral loads across multiple tissues. By day\u200910 postinfection, markedly elevated levels of pro\u2010inflammatory cytokines were detected in plasma, whereas anti\u2010inflammatory cytokines remained largely uninduced. We found that the infection of severely immunodeficient mice with mpox virus results in dose\u2010dependent lethality, persistent high viral loads, and a pronounced pro\u2212\/anti\u2010inflammatory imbalance. These findings provide important insights into the pathogenesis of mpox in immunocompromised populations and develop a practical animal model for evaluating therapeutic interventions.\n                  <\/jats:p>","DOI":"10.1002\/ame2.70227","type":"journal-article","created":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T05:46:42Z","timestamp":1779428802000},"page":"1047-1055","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dose\u2010dependent pathogenicity and inflammatory imbalance in severely immunodeficient mice infected with mpox virus"],"prefix":"10.1002","volume":"9","author":[{"given":"Na","family":"Li","sequence":"first","affiliation":[{"name":"NHC Key Laboratory of Human Disease Comparative Medicine, National Center of Technology Innovation for Animal Model Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences, Peking Union Medical College  Beijing 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Model Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences, Peking Union Medical College  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahan","family":"Lu","sequence":"additional","affiliation":[{"name":"NHC Key Laboratory of Human Disease Comparative Medicine, National Center of Technology Innovation for Animal Model Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences, Peking Union Medical College  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongzhi","family":"Hou","sequence":"additional","affiliation":[{"name":"NHC Key Laboratory of Human Disease Comparative Medicine, National Center of Technology Innovation for Animal Model Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences, Peking Union Medical College  Beijing 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