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These mutations are located in the viral genes encoding the RdRp and the non-structural protein NSs. This paper shows the results obtained after the subcutaneous inoculation of ZH548-rA2 in adult sheep and the subsequent challenge with the parental virus (ZH548-rC1). Inoculation with the ZH548-rA2 virus caused no detectable clinical or pathological effect in sheep, whereas inoculation of the parental rC1 virus caused lesions compatible with viral infection characterised by the presence of scattered hepatic necrosis. Viral infection was confirmed via immunohistochemistry, with hepatocytes within the necrotic foci appearing as the main cells immunolabelled against viral antigen. Furthermore, the inoculation of sheep with the rA2 virus prevented the liver damage expected after rC1 virus inoculation, suggesting a protective efficacy in sheep which correlated with the induction of both humoral and cell-mediated immune responses.<\/jats:p>","DOI":"10.3390\/v16010087","type":"journal-article","created":{"date-parts":[[2024,1,5]],"date-time":"2024-01-05T05:12:17Z","timestamp":1704431537000},"page":"87","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Safety and Efficacy upon Infection in Sheep with Rift Valley Fever Virus ZH548-rA2, a Triple Mutant Rescued Virus"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3548-037X","authenticated-orcid":false,"given":"Sandra","family":"Moreno","sequence":"first","affiliation":[{"name":"Centro de Investigaci\u00f3n en Sanidad Animal (CISA), Instituto Nacional de Investigaci\u00f3n y Tecnolog\u00eda Agraria y Alimentaria, Consejo Superior de Investigaciones Cient\u00edficas (INIA-CSIC), Valdeolmos, 28130 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gema","family":"Lorenzo","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n en Sanidad Animal (CISA), Instituto Nacional de Investigaci\u00f3n y Tecnolog\u00eda Agraria y Alimentaria, Consejo Superior de Investigaciones Cient\u00edficas (INIA-CSIC), Valdeolmos, 28130 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1lvaro","family":"L\u00f3pez-Vali\u00f1as","sequence":"additional","affiliation":[{"name":"Centre de Recerca en Sanitat Animal (CReSA), Institut de Recerca i Tecnologia Agroaliment\u00e0ries (IRTA), Bellaterra, 08193 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuria","family":"de la Losa","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n en Sanidad Animal (CISA), Instituto Nacional de Investigaci\u00f3n y Tecnolog\u00eda Agraria y Alimentaria, Consejo Superior de Investigaciones Cient\u00edficas (INIA-CSIC), Valdeolmos, 28130 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celia","family":"Alonso","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n en Sanidad Animal (CISA), Instituto Nacional de Investigaci\u00f3n y Tecnolog\u00eda Agraria y Alimentaria, Consejo Superior de Investigaciones Cient\u00edficas (INIA-CSIC), Valdeolmos, 28130 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Charro","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n en Sanidad Animal (CISA), Instituto Nacional de Investigaci\u00f3n y Tecnolog\u00eda Agraria y Alimentaria, Consejo Superior de Investigaciones Cient\u00edficas (INIA-CSIC), Valdeolmos, 28130 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9890-7695","authenticated-orcid":false,"given":"Jos\u00e9 I.","family":"N\u00fa\u00f1ez","sequence":"additional","affiliation":[{"name":"Centre de Recerca en Sanitat Animal (CReSA), Institut de Recerca i Tecnologia Agroaliment\u00e0ries (IRTA), Bellaterra, 08193 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7202-6475","authenticated-orcid":false,"given":"Pedro J.","family":"S\u00e1nchez-Cord\u00f3n","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n en Sanidad Animal (CISA), Instituto Nacional de Investigaci\u00f3n y Tecnolog\u00eda Agraria y Alimentaria, Consejo Superior de Investigaciones Cient\u00edficas (INIA-CSIC), Valdeolmos, 28130 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0801-9166","authenticated-orcid":false,"given":"Bel\u00e9n","family":"Borrego","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n en Sanidad Animal (CISA), Instituto Nacional de Investigaci\u00f3n y Tecnolog\u00eda Agraria y Alimentaria, Consejo Superior de Investigaciones Cient\u00edficas (INIA-CSIC), Valdeolmos, 28130 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro","family":"Brun","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n en Sanidad Animal (CISA), Instituto Nacional de Investigaci\u00f3n y Tecnolog\u00eda Agraria y Alimentaria, Consejo Superior de Investigaciones Cient\u00edficas (INIA-CSIC), Valdeolmos, 28130 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Napp, S., Chevalier, V., Busquets, N., Calistri, P., Casal, J., Attia, M., Elbassal, R., Hosni, H., Farrag, H., and Hassan, N. 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