Determining Tropism and Mechanisms of Ebola Virus Entry in Placental Tissues

确定埃博拉病毒进入胎盘组织的趋向性和机制

• 批准号: 10605584
• 负责人: Hanora Anne Marie Van Ert
• 金额: $ 3.9万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-11-15 至 2025-07-14
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10605584
• 关键词: 2019-nCoV; Academic Medical Centers; Africa; Antigens; Binding; C Type Lectin Receptors; C-Type Lectins; Cell membrane; Cell surface; Cells; Cessation of life; Chorionic villi; Clinical; Communicable Diseases; Containment; Data; Dendritic Cells; Development; Discipline of obstetrics; Disease Outbreaks; Ebola Hemorrhagic Fever; Ebola virus; Endosomes; Endothelial Cells; Environment; Epithelial Cells; Evaluation; Experimental Animal Model; Family member; Fellowship; Fetal Death; Fetal Development; Fetal Tissues; Fetus; Fibroblasts; Filoviridae Infections; Filovirus; Funding; Future; Glycoproteins; Goals; Health; Health Sciences; Human; Immune response; Immunology; In Vitro; Individual; Infection; Iowa; Knowledge; Macrophage; Maternal-Fetal Exchange; Maternal-fetal medicine; Mentors; Mentorship; Microbiology; Modeling; Mothers; Outcome; Pathogenesis; Pathology; Personal Satisfaction; Persons; Phosphatidylserines; Physicians; Placenta; Play; Polysaccharides; Population; Positioning Attribute; Predisposition; Pregnancy; Pregnant Women; Process; Production; Productivity; RNA Viruses; Reproductive Health; Research; Research Design; Research Personnel; Residencies; Role; Route; Scientist; Series; Source; Syncytiotrophoblast; Techniques; Testing; Therapeutic; Tissues; Training; Transportation; Treatment Protocols; Tropism; Universities; Viral; Viral Hemorrhagic Fevers; Viral Pathogenesis; Viremia; Virion; Virus; Virus Diseases; Virus Replication; Woman; Work; Zaire Ebola virus; Zika Virus; cell type; emerging pathogen; experience; fetal; fetal loss; fetus cell; glycosylation; human morbidity; human mortality; improved; in vivo; insight; late endosome; member; monocyte; neonatal death; neonate; pathogen; peripheral blood; phosphatidylserine receptor; placental infection; receptor; skills; symposium; tenure track; therapeutic development; training opportunity; transmission process; viral RNA; viral transmission; virology

Project Summary/Abstract During pregnancy, viral infections in the mother may have catastrophic effects on her health, or on the viability of the developing fetus. Recently, emerging pathogen outbreaks such as those involving Zika Virus (ZIKV), SARS-CoV-2 or Ebola Virus (EBOV) have highlighted how understudied the role of the placenta is in transmission of viral infections. This project specifically focuses on the cell tropism of EBOV during pregnancy. Ebola Virus Disease (EVD) is caused by infection with EBOV or other members within the Ebolavirus genus. During pregnancy, EVD results in loss of ~100% of fetuses or neonates with or without the additional loss of the mother. Anecdotal data from EBOV outbreaks in Africa suggest that EBOV directly infects placental tissues, thus transmitting virus to the fetal compartment, but rigorous experimental evaluation of placental infection has not been performed; the tropism of EBOV for placental cells, mechanisms of cellular entry, and route of infection from mother to fetus are currently unknown. Aim 1 will examine tropism of EBOV in placental tissues. Further, as EBOV has been shown to bind to and internalize into many cell types via interactions with phosphatidylserine (PS) receptors, Aim 2 studies will evaluate the role of three PS receptors on EBOV infection of the placenta and fetus. These studies will be performed using two low containment EBOV model viruses, rVSV-EBOV-GP-GFP and EBOV ΔVP30, that have been used extensively to understand filovirus tropism and receptor usage. The knowledge gained from these rigorously designed studies will elucidate cell populations within the placenta infected and important for fetal transmission as a first step toward understanding the catastrophic pathogenesis of EVD in pregnancy. Additionally, this work will provide insights for the development of therapeutic treatment options to improve the maternal and fetal outcomes of EVD. The experiences, techniques, mentoring, and concepts in this proposal were specifically tailored to Ms. Hanora Van Ert and her training goals. As a developing researcher passionate about improving the health and wellbeing of pregnant women, Ms. Van Ert is currently completing her studies in the MSTP at University of Iowa under the scientific mentorship of Dr. Wendy Maury and Dr. Mark Santillan receiving individualized training at the intersection of virology, immunology, and reproductive health sciences to supply her passion with the necessary research skills. Additionally, the MSTP, Department of OB/Gyn, and Department of Microbiology and Immunology at the University of Iowa provide ample training opportunities in the forms of seminar series, funding for attending academic conferences, opportunities to meet prominent people in the fields of virology, immunology, and OB/Gyn, as well as a supportive and collaborative research environment. Ms. Van Ert will complete her MSTP training and pursue a research residency in OB/Gyn, clinical Maternal- fetal medicine fellowship, and ultimately tenure track position at an academic medical center to continue investigating the host-pathogen immune response at the maternal-fetal interface within the placenta.

项目摘要/摘要 怀孕期间，母亲的病毒感染可能会对她的健康或对她的健康产生灾难性影响 发育中的胎儿的生存力，新兴的病原体武器 （ZIKV），SARS-COV-2或埃博拉病毒（EBOV）Hight强调了胎盘的作用如何研究 病毒感染的传播。 埃博拉病毒疾病（EVD）是由EBOV或EBLAVIRUS属内其他成员感染引起的。 在怀孕期间，EVD导致约100％的胎儿或新生儿损失，或者没有额外的损失 母亲。 组织，从而将病毒传播到胎儿室，但胎盘的严格实验评估 尚未进行感染； 目前从母亲到胎儿的感染途径未知。 进一步的组织，因为EBOV已通过与 磷脂酰丝氨酸（PS）受体，AIM 2研究将评估三个PS受体ONBOV的作用 胎盘和胎儿的感染将使用两个低遏制模型进行 病毒，RVSV-EBOV-GP-GFP和EBOVΔVP30，已广泛用于了解FILOVIVIRUS 对流和受体的使用。 胎盘内感染的种群，对于胎儿传播很重要，作为迈向的第一步 理解EVD的灾难性发病机理。 为了开发治疗方案，以改善孕产妇和胎儿。 该提案中的经验，技术，指导和概念是针对MS量身定制的。 Hanora van Ert及其培训目标。 孕妇的健康，范·埃特（Van Ert）女士目前正在大学中的MSTP学习 爱荷华州在温迪·梅里（Wendy Mairy）博士和马克·桑蒂兰（Mark Santillan）博士的科学指导下接受个性化 在病毒学，免疫学和生殖健康科学的交叉点上培训，以支持她的热情 凭借必要的研究技能。 爱荷华大学的微生物学和免疫学提供了充足的培训机会 研讨会系列，获得学术会议的资金，与您结识的人的机会 病毒学，免疫学和OB/GYN领域，以及支持性和协作性研究的环境。 Van Ert女士将完成她的MSTP培训，并在OB/GYN，临床母亲的OB/GYN进行研究居住 胎儿医学奖学金，并最终在学院医学上担任统治轨道职位 研究胎盘内母性界面处的宿主 - 病原体免疫反应。