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Maternal ZIKV infection during pregnancy can spread to the placenta and fetus causing severe neurological defects and infants born with microcephaly. Here, we investigated ZIKV infection and the cellular innate antiviral immune response in first trimester human placental explant cultures and isolated primary villus cytotrophoblasts (CTBs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Placentas were obtained with informed consent from women undergoing elective pregnancy termination and either cultured as placental explants or used to isolate primary CTBs. Explants and CTBs were both infected with ZIKV (PRVABC59), and samples evaluated for infection by qRT-PCR, viral plaque and ELISA assays, and immunohistochemical or immunocytochemical staining.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We demonstrate robust infection and production of ZIKV in placental explant and CTB cultures. Both displayed delayed upregulation of interferons (IFN), most notably IFN\u03b2 and IFN\u03bb2\/3, and a panel of interferon stimulated genes (ISG)\n                      <jats:italic>(IFI6<\/jats:italic>\n                      ,\n                      <jats:italic>IFIT1<\/jats:italic>\n                      ,\n                      <jats:italic>IFIT2<\/jats:italic>\n                      ,\n                      <jats:italic>IFITM1<\/jats:italic>\n                      ,\n                      <jats:italic>ISG15<\/jats:italic>\n                      ,\n                      <jats:italic>MX1<\/jats:italic>\n                      ,\n                      <jats:italic>RSAD<\/jats:italic>\n                      ). Stimulation of explants and CTBs with the dsRNA mimic poly(I: C), caused immediate\n                      <jats:italic>IFN<\/jats:italic>\n                      and\n                      <jats:italic>ISG<\/jats:italic>\n                      upregulation, demonstrating the first trimester placenta is innate immune competent. This suggests that either ZIKV blocks the early innate response, or the placental response is inherently hindered.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Together these data show that first trimester placenta is susceptible to ZIKV infection which induces a delayed type III IFN antiviral response. This delay likely creates an environment favourable to ZIKV replication and dissemination across the early gestation placenta to fetal tissue, causing pathologies associated with congenital ZIKV syndrome.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12985-025-02729-3","type":"journal-article","created":{"date-parts":[[2025,4,19]],"date-time":"2025-04-19T01:12:56Z","timestamp":1745025176000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["The first trimester human placenta responds to Zika virus infection inducing an interferon (IFN) and antiviral interferon stimulated gene (ISG) response"],"prefix":"10.1186","volume":"22","author":[{"given":"Kylie H.","family":"Van der Hoek","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanja","family":"Jankovic-Karasoulos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dylan","family":"McCullough","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa C.","family":"Coldbeck-Shackley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas S.","family":"Eyre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire T.","family":"Roberts","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael R.","family":"Beard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,4,19]]},"reference":[{"issue":"24","key":"2729_CR1","doi-asserted-by":"publisher","first-page":"2321","DOI":"10.1056\/NEJMoa1602412","volume":"375","author":"P Brasil","year":"2016","unstructured":"Brasil P, Pereira JP Jr., Moreira ME, Ribeiro Nogueira RM, Damasceno L, Wakimoto M, et al. 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