{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T14:46:03Z","timestamp":1787064363954,"version":"build-2736575974"},"reference-count":71,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2022,10,18]],"date-time":"2022-10-18T00:00:00Z","timestamp":1666051200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"DFG Research Training Group 2485 VIPER","award":["LARISSA"],"award-info":[{"award-number":["LARISSA"]}]},{"name":"Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)-491094227 \u201cOpen Access Publication Funding\u201d","award":["LARISSA"],"award-info":[{"award-number":["LARISSA"]}]},{"name":"University of Veterinary Medicine Hannover, Foundation","award":["LARISSA"],"award-info":[{"award-number":["LARISSA"]}]},{"name":"Alexander von Humboldt Foundation","award":["LARISSA"],"award-info":[{"award-number":["LARISSA"]}]},{"DOI":"10.13039\/100016302","name":"CEPI-funded project","doi-asserted-by":"publisher","award":["LARISSA"],"award-info":[{"award-number":["LARISSA"]}],"id":[{"id":"10.13039\/100016302","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Rift Valley fever (RVF) is a zoonotic and emerging disease, caused by the RVF virus (RVFV). In ruminants, it leads to \u201cabortion storms\u201d and enhanced mortality rates in young animals, whereas in humans it can cause symptoms like severe hemorrhagic fever or encephalitis. The role of the innate and adaptive immune response in disease initiation and progression is still poorly defined. The present study used the attenuated RVFV strain clone 13 to investigate viral spread, tissue tropism, and histopathological lesions after intranasal infection in C57BL\/6 wild type (WT) and type I interferon (IFN-I) receptor I knockout (IFNAR\u2212\/\u2212) mice. In WT mice, 104 PFU RVFV (high dose) resulted in a fatal encephalitis, but no hepatitis 7\u201311 days post infection (dpi), whereas 103 PFU RVFV (low dose) did not cause clinical disease or significant histopathological lesions in liver and the central nervous system (CNS). In contrast, IFNAR\u2212\/\u2212 mice infected with 103 PFU RVFV developed hepatocellular necrosis resulting in death at 2\u20135 dpi and lacked encephalitis. These results show that IFNAR signaling prevents systemic spread of the attenuated RVFV strain clone 13, but not the dissemination to the CNS and subsequent fatal disease. Consequently, neurotropic viruses may be able to evade antiviral IFN-I signaling pathways by using the transneuronal instead of the hematogenous route.<\/jats:p>","DOI":"10.3390\/ijms232012492","type":"journal-article","created":{"date-parts":[[2022,10,19]],"date-time":"2022-10-19T00:58:51Z","timestamp":1666141131000},"page":"12492","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Intact Type I Interferon Receptor Signaling Prevents Hepatocellular Necrosis but Not Encephalitis in a Dose-Dependent Manner in Rift Valley Fever Virus Infected Mice"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6271-5253","authenticated-orcid":false,"given":"Lukas Mathias","family":"Michaely","sequence":"first","affiliation":[{"name":"Department of Pathology, University of Veterinary Medicine Hannover, Foundation, 30559 Hannover, Germany"},{"name":"Center for Systems Neuroscience, 30559 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lukas","family":"Schuwerk","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Veterinary Medicine Hannover, Foundation, 30559 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8822-4409","authenticated-orcid":false,"given":"Lisa","family":"Allnoch","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Veterinary Medicine Hannover, Foundation, 30559 Hannover, Germany"},{"name":"Center for Systems Neuroscience, 30559 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen","family":"Sch\u00f6n","sequence":"additional","affiliation":[{"name":"Institute for Parasitology, University of Veterinary Medicine Hannover, Foundation, 30559 Hannover, Germany"},{"name":"Research Center for Emerging Infections and Zoonoses (RIZ), University of Veterinary Medicine Hannover, Foundation, 30559 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inken","family":"Waltl","sequence":"additional","affiliation":[{"name":"Institute for Experimental Infection Research, TWINCORE, Centre for Experimental and Clinical Infection Research, a Joint Venture between the Helmholtz Centre for Infection Research and the Hannover Medical School, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pia-Katharina","family":"Larsen","sequence":"additional","affiliation":[{"name":"Institute for Experimental Infection Research, TWINCORE, Centre for Experimental and Clinical Infection Research, a Joint Venture between the Helmholtz Centre for Infection Research and the Hannover Medical School, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Pavlou","sequence":"additional","affiliation":[{"name":"Center for Systems Neuroscience, 30559 Hannover, Germany"},{"name":"Institute for Experimental Infection Research, TWINCORE, Centre for Experimental and Clinical Infection Research, a Joint Venture between the Helmholtz Centre for Infection Research and the Hannover Medical School, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6631-2096","authenticated-orcid":false,"given":"Chittappen Kandiyil","family":"Prajeeth","sequence":"additional","affiliation":[{"name":"Research Center for Emerging Infections and Zoonoses (RIZ), University of Veterinary Medicine Hannover, Foundation, 30559 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1921-4581","authenticated-orcid":false,"given":"Guus F.","family":"Rimmelzwaan","sequence":"additional","affiliation":[{"name":"Research Center for Emerging Infections and Zoonoses (RIZ), University of Veterinary Medicine Hannover, Foundation, 30559 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie C.","family":"Becker","sequence":"additional","affiliation":[{"name":"Institute for Parasitology, University of Veterinary Medicine Hannover, Foundation, 30559 Hannover, Germany"},{"name":"Research Center for Emerging Infections and Zoonoses (RIZ), University of Veterinary Medicine Hannover, Foundation, 30559 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0503-9564","authenticated-orcid":false,"given":"Ulrich","family":"Kalinke","sequence":"additional","affiliation":[{"name":"Center for Systems Neuroscience, 30559 Hannover, Germany"},{"name":"Institute for Experimental Infection Research, TWINCORE, Centre for Experimental and Clinical Infection Research, a Joint Venture between the Helmholtz Centre for Infection Research and the Hannover Medical School, 30625 Hannover, 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":"Department of Pathology, University of Veterinary Medicine Hannover, Foundation, 30559 Hannover, Germany"},{"name":"Center for Systems Neuroscience, 30559 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7973-7405","authenticated-orcid":false,"given":"Ingo","family":"Gerhauser","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Veterinary Medicine Hannover, Foundation, 30559 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.cll.2017.01.004","article-title":"Rift Valley 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