{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T17:45:08Z","timestamp":1789839908777,"version":"4.0.1"},"reference-count":66,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,11,10]],"date-time":"2022-11-10T00:00:00Z","timestamp":1668038400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"IMI and the European Commission","award":["115760"],"award-info":[{"award-number":["115760"]}]},{"name":"Center Systems Neuroscience of the University of Veterinary Medicine Hannover","award":["115760"],"award-info":[{"award-number":["115760"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Rift Valley fever phlebovirus (RVFV) causes Rift Valley fever (RVF), an emerging zoonotic disease that causes abortion storms and high mortality rates in young ruminants as well as severe or even lethal complications in a subset of human patients. This study investigates the pathomechanism of intranuclear inclusion body formation in severe RVF in a mouse model. Liver samples from immunocompetent mice infected with virulent RVFV 35\/74, and immunodeficient knockout mice that lack interferon type I receptor expression and were infected with attenuated RVFV MP12 were compared to livers from uninfected controls using histopathology and immunohistochemistry for RVFV nucleoprotein, non-structural protein S (NSs) and pro-apoptotic active caspase-3. Histopathology of the livers showed virus-induced, severe hepatic necrosis in both mouse strains. However, immunohistochemistry and immunofluorescence revealed eosinophilic, comma-shaped, intranuclear inclusions and an intranuclear (co-)localization of RVFV NSs and active caspase-3 only in 35\/74-infected immunocompetent mice, but not in MP12-infected immunodeficient mice. These results suggest that intranuclear accumulation of RVFV 35\/74 NSs is involved in nuclear translocation of active caspase-3, and that nuclear NSs and active caspase-3 are involved in the formation of the light microscopically visible inclusion bodies.<\/jats:p>","DOI":"10.3390\/v14112487","type":"journal-article","created":{"date-parts":[[2022,11,10]],"date-time":"2022-11-10T19:18:29Z","timestamp":1668107909000},"page":"2487","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Rift Valley Fever Virus Non-Structural Protein S Is Associated with Nuclear Translocation of Active Caspase-3 and Inclusion Body Formation"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6271-5253","authenticated-orcid":false,"given":"Lukas Mathias","family":"Michaely","sequence":"first","affiliation":[{"name":"Center of Systems Neuroscience, Department of Pathology, University of Veterinary 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Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felicitas","family":"von Arnim","sequence":"additional","affiliation":[{"name":"Institute of Novel and Emerging Diseases, Friedrich-Loeffler-Institute, Insel Riems, 17493 Greifswald, Germany"},{"name":"Partner Site Hamburg-L\u00fcbeck-Borstel-Riems, German Center for Infection Research (DZIF), Insel Riems, 17493 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3229-8377","authenticated-orcid":false,"given":"Markus","family":"Keller","sequence":"additional","affiliation":[{"name":"Institute of Novel and Emerging Diseases, Friedrich-Loeffler-Institute, Insel Riems, 17493 Greifswald, Germany"},{"name":"Partner Site Hamburg-L\u00fcbeck-Borstel-Riems, German Center for Infection Research (DZIF), Insel Riems, 17493 Greifswald, 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Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Gutjahr","sequence":"additional","affiliation":[{"name":"Institute of Novel and Emerging Diseases, Friedrich-Loeffler-Institute, Insel Riems, 17493 Greifswald, Germany"},{"name":"Partner Site Hamburg-L\u00fcbeck-Borstel-Riems, German Center for Infection Research (DZIF), Insel Riems, 17493 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8151-5644","authenticated-orcid":false,"given":"Wolfgang","family":"Baumg\u00e4rtner","sequence":"additional","affiliation":[{"name":"Center of Systems Neuroscience, Department of Pathology, University of Veterinary Medicine Hannover, Foundation, 30559 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0215-185X","authenticated-orcid":false,"given":"Martin 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Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.cll.2017.01.004","article-title":"Rift Valley Fever","volume":"37","author":"Hartman","year":"2017","journal-title":"Clin. 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