Rift Valley fever virus targets the maternal-foetal interface in ovine and human placentas

BackgroundRift Valley fever virus (RVFV) is an arbovirus of the order Bunyavirales that causes severe disease in ruminants and humans. Outbreaks in sheep herds are characterised by newborn fatalities and abortion storms. The association of RVFV infections with abortions of ovines and other ruminants is well recognized, whereas the pathology resulting in abortion has remained undescribed. Accumulating evidence suggests that RVFV is abortogenic in humans as well, warranting more research on the interaction of RVFV with the ruminant and human placenta.Methodology/Principal findingsPregnant ewes were inoculated with a highly virulent strain of RVFV and necropsied at different days post infection. Tissues were collected and analysed by PCR, virus isolation, and immunohistochemistry. The results show that RVFV replicates efficiently in maternal placental epithelial cells before the virus infects foetal trophoblasts. Moreover, the virus was shown to bypass the maternal epithelial cell layer by directly targeting foetal trophoblasts in the haemophagous zone, a region of the ovine placenta where maternal blood is in direct contact with foetal cells. Abortion was associated with widespread necrosis of placental tissues accompanied with severe haemorrhages. Experiments with human placental explants revealed that the same virus strain replicates efficiently in both cyto- and syncytiotrophoblasts.Conclusions/SignificanceThis study demonstrates that RVFV targets the foetal-maternal interface in both ovine and human placentas. The virus was shown to cross the ovine placental barrier via two distinct routes, ultimately resulting in placental and foetal demise followed by abortion. Our finding that RVFV replicates efficiently in human trophoblasts underscores the risk of RVFV infection for human pregnancy.背景：裂谷热病毒（Rift Valley fever virus, RVFV）属于布尼亚病毒目（Bunyavirales）的虫媒病毒（arbovirus），可在反刍动物与人类中引发重症疾病。羊群暴发疫情时，典型特征为新生羔羊死亡与流产风暴。RVFV感染与绵羊及其他反刍动物流产的关联已得到学界广泛认可，但介导流产的病理机制至今仍未阐明。越来越多的研究证据表明，RVFV对人类同样具有致流产性，因此亟需开展更多关于RVFV与反刍动物及人类胎盘相互作用的相关研究。 研究方法与主要发现：本研究对怀孕母羊接种高致病性RVFV毒株，并于感染后的不同天数进行剖检。采集组织样本后，通过聚合酶链式反应（PCR）、病毒分离以及免疫组织化学（immunohistochemistry）技术开展分析。结果显示，RVFV在感染胎儿滋养层细胞（foetal trophoblasts）之前，可在母体胎盘上皮细胞中高效复制。此外，研究发现病毒可通过直接靶向吸血区（haemophagous zone）的胎儿滋养层细胞，绕过母体上皮细胞层——绵羊胎盘的该区域中，母体血液与胎儿细胞直接接触。流产症状与胎盘组织广泛坏死及严重出血密切相关。利用人类胎盘外植体（placental explants）开展的实验显示，同一毒株可在细胞滋养层与合体滋养层中高效复制。 结论与意义：本研究证实，RVFV可靶向绵羊与人类胎盘的母胎界面。研究表明，病毒可通过两条不同途径跨越绵羊胎盘屏障，最终导致胎盘与胎儿死亡并引发流产。我们发现RVFV可在人类滋养层细胞中高效复制，这一发现凸显了RVFV感染对人类妊娠的潜在风险。