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Using sheep and human placenta explant cultures, we sought to identify tissues at the maternal\u2013fetal interface targeted by RVFV. Sheep villi and fetal membranes were highly permissive to RVFV infection resulting in markedly higher virus titers than human cultures. Sheep cultures were most permissive to wild-type RVFV and \u0394NSm infection, while live-attenuated RVFV vaccines (LAVs; MP-12, \u0394NSs, and \u0394NSs\/\u0394NSm) exhibited reduced replication. The human fetal membrane restricted wild-type and LAV replication, and when infection occurred, it was prominent on the maternal-facing side. Type I and type III interferons were induced in human villi exposed to LAVs lacking the NSs protein. This study supports the use of sheep and human placenta explants to understand vertical transmission of RVFV in mammals and whether LAVs are attenuated at the maternal\u2013fetal interface.<\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>A direct comparison of replication of Rift Valley fever virus (RVFV) in sheep and human placental explants reveals comparative efficiencies and permissivity to infection and replication. Vaccine strains of RVFV demonstrated reduced infection and replication capacity in the mammalian placenta. This study represents the first direct cross-host comparison of the vertical transmission capacity of this high-priority emerging mosquito-transmitted virus.<\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/jvi.00983-24","type":"journal-article","created":{"date-parts":[[2024,7,17]],"date-time":"2024-07-17T09:00:43Z","timestamp":1721206843000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":4,"title":["Vaccine strains of Rift Valley fever virus exhibit attenuation at the maternal\u2013fetal placental interface"],"prefix":"10.1128","volume":"98","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9211-7908","authenticated-orcid":true,"given":"Cynthia M.","family":"McMillen","sequence":"first","affiliation":[{"name":"University of Pittsburgh, Center for Vaccine Research, Pittsburgh, Pennsylvania, USA"},{"name":"Department of Infectious Diseases and Microbiology, University of Pittsburgh, School of Public Health, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Megli","sequence":"additional","affiliation":[{"name":"Division of Maternal-Fetal Medicine, Division of Reproductive Infectious Disease, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine and the Magee-Womens Research Institute, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Radisic","sequence":"additional","affiliation":[{"name":"One Health Institute, School of Veterinary Medicine, University of California, Davis, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren B.","family":"Skvarca","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan M.","family":"Hoehl","sequence":"additional","affiliation":[{"name":"University of Pittsburgh, Center for Vaccine Research, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devin A.","family":"Boyles","sequence":"additional","affiliation":[{"name":"University of Pittsburgh, Center for Vaccine Research, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jackson J.","family":"McGaughey","sequence":"additional","affiliation":[{"name":"University of Pittsburgh, Center for Vaccine Research, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian H.","family":"Bird","sequence":"additional","affiliation":[{"name":"One Health Institute, School of Veterinary Medicine, University of California, Davis, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6764-7536","authenticated-orcid":true,"given":"Anita K.","family":"McElroy","sequence":"additional","affiliation":[{"name":"University of Pittsburgh, Center for Vaccine Research, Pittsburgh, Pennsylvania, USA"},{"name":"Department of Pediatrics, Division of Pediatric Infectious Disease, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0857-2973","authenticated-orcid":true,"given":"Amy L.","family":"Hartman","sequence":"additional","affiliation":[{"name":"University of Pittsburgh, Center for Vaccine Research, Pittsburgh, Pennsylvania, USA"},{"name":"Department of Infectious Diseases and Microbiology, University of Pittsburgh, School of Public Health, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1186\/2193-1801-2-549"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0007898"},{"key":"e_1_3_5_4_2","first-page":"205","article-title":"The pathology of Rift Valley fever. 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