{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T14:11:21Z","timestamp":1787062281433,"version":"build-2736575974"},"reference-count":93,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,2,8]],"date-time":"2022-02-08T00:00:00Z","timestamp":1644278400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010767","name":"Innovative Medicines Initiative","doi-asserted-by":"publisher","award":["115760"],"award-info":[{"award-number":["115760"]}],"id":[{"id":"10.13039\/501100010767","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Rift Valley fever (RVF) is a zoonotic disease caused by RVF Phlebovirus (RVFV). The RVFV MP-12 vaccine strain is known to exhibit residual virulence in the case of a deficient interferon type 1 response. The hypothesis of this study is that virus replication and severity of lesions induced by the MP-12 strain in immunocompromised mice depend on the specific function of the disturbed pathway. Therefore, 10 strains of mice with deficient innate immunity (B6-IFNARtmAgt, C.129S7(B6)-Ifngtm1Ts\/J, B6-TLR3tm1Flv, B6-TLR7tm1Aki, NOD\/ShiLtJ), helper T-cell- (CD4tm1Mak), cytotoxic T-cell- (CD8atm1Mak), B-cell- (Igh-Jtm1DhuN?+N2), combined T- and B-cell- (NU\/J) and combined T-, B-, natural killer (NK) cell- and macrophage-mediated immunity (NOD.Cg-PrkdcscidIl2rgtm1WjI\/SzJ (NSG) mice) were subcutaneously infected with RVFV MP-12. B6-IFNARtmAgt mice were the only strain to develop fatal disease due to RVFV-induced severe hepatocellular necrosis and apoptosis. Notably, no clinical disease and only mild multifocal hepatocellular necrosis and apoptosis were observed in NSG mice, while immunohistochemistry detected the RVFV antigen in the liver and the brain. No or low virus expression and no lesions were observed in the other mouse strains. Conclusively, the interferon type 1 response is essential for early control of RVFV replication and disease, whereas functional NK cells, macrophages and lymphocytes are essential for virus clearance.<\/jats:p>","DOI":"10.3390\/v14020350","type":"journal-article","created":{"date-parts":[[2022,2,8]],"date-time":"2022-02-08T23:42:20Z","timestamp":1644363740000},"page":"350","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["NSG-Mice Reveal the Importance of a Functional Innate and Adaptive Immune Response to Overcome RVFV Infection"],"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":"Department of Pathology, University of Veterinary Medicine Hannover, Foundation, B\u00fcnteweg 17, 30559 Hannover, Germany"},{"name":"Center for Systems Neuroscience Hannover, University of Veterinary Medicine Hannover, Foundation, B\u00fcnteweg 2, 30559 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5298-5919","authenticated-orcid":false,"given":"Melanie","family":"Rissmann","sequence":"additional","affiliation":[{"name":"Institute of Novel and Emerging Infectious Diseases, Friedrich-Loeffler-Institut, S\u00fcdufer 10, 17493 Greifswald-Insel Riems, 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 Infectious Diseases, Friedrich-Loeffler-Institut, S\u00fcdufer 10, 17493 Greifswald-Insel Riems, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"K\u00f6nig","sequence":"additional","affiliation":[{"name":"Institute of Novel and Emerging Infectious Diseases, Friedrich-Loeffler-Institut, S\u00fcdufer 10, 17493 Greifswald-Insel Riems, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felicitas","family":"von Arnim","sequence":"additional","affiliation":[{"name":"Institute of Novel and Emerging Infectious Diseases, Friedrich-Loeffler-Institut, S\u00fcdufer 10, 17493 Greifswald-Insel Riems, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1197-8288","authenticated-orcid":false,"given":"Martin","family":"Eiden","sequence":"additional","affiliation":[{"name":"Institute of Novel and Emerging Infectious Diseases, Friedrich-Loeffler-Institut, S\u00fcdufer 10, 17493 Greifswald-Insel Riems, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl","family":"Rohn","sequence":"additional","affiliation":[{"name":"Institute for Biometry, Epidemiology and Information Processing, University of Veterinary Medicine Hannover, Foundation, B\u00fcnteweg 2, 30559 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, B\u00fcnteweg 17, 30559 Hannover, Germany"},{"name":"Center for Systems Neuroscience Hannover, University of Veterinary Medicine Hannover, Foundation, B\u00fcnteweg 2, 30559 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0215-185X","authenticated-orcid":false,"given":"Martin","family":"Groschup","sequence":"additional","affiliation":[{"name":"Institute of Novel and Emerging Infectious Diseases, Friedrich-Loeffler-Institut, S\u00fcdufer 10, 17493 Greifswald-Insel Riems, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9403-1224","authenticated-orcid":false,"given":"Reiner","family":"Ulrich","sequence":"additional","affiliation":[{"name":"Institute of Veterinary-Pathology, Faculty of Veterinary Medicine, Leipzig University, 04103 Leipzig, Germany"},{"name":"Department of Experimental Animal Facilities and Biorisk Management, Friedrich-Loeffler-Institut, S\u00fcdufer 10, 17493 Greifswald-Insel Riems, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1177\/0300985819826308","article-title":"Rift Valley Fever: An Ancient Plague on Its Way Out of Africa?","volume":"56","author":"Ulrich","year":"2019","journal-title":"Vet. 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