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

基本信息

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
项目类别：
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

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

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项目摘要

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能力。最近，新兴的病原体暴发，例如涉及寨卡病毒的病原体（ZIKV），SARS-COV-2或EBOLA病毒（EBOV）强调了Plopeta在病毒感染的传播。该项目特别关注怀孕期间EBOV的细胞向性。埃博拉病毒疾病（EVD）是由EBOV或埃博拉病毒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。非洲EBOV暴发的轶事数据表明，EBOV直接感染了PlaceAl 组织，从而将病毒传播到胎儿室，但对斑点的严格实验评估尚未进行感染； EBOV用于占地细胞的向量，细胞进入机制和目前尚不清楚从母亲到胎儿的感染途径。 AIM 1将检查EBOV的TROPISM 组织。此外，由于已显示EBOV通过与磷脂酰丝氨酸（PS）受体，AIM 2研究将评估三个PS受体在EBOV上的作用胎盘和胎儿的感染。这些研究将使用两个低遏制EBOV模型进行病毒，RVSV-EBOV-GP-GFP和EBOVΔVP30，已广泛用于了解filevirus 向上主义和受体用法。从这些严格设计的研究中获得的知识将阐明细胞胎盘中的种群感染了胎儿传播，这是迈向胎儿传播的第一步了解怀孕中EVD的灾难性发病机理。此外，这项工作将提供见解为了开发治疗方案，以改善EVD的产妇和胎儿结局。该提案中的经验，技术，指导和概念是专门针对女士的。 Hanora van Ert及其训练目标。作为一名发展的研究人员，热衷于改善健康和孕妇的健康，范·埃特（Van Ert）女士目前正在大学的MSTP学习爱荷华州在温迪·莫里（Wendy Maury）和马克·桑蒂兰（Mark Santillan）博士的科学心态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，以供应她的激情具有必要的研究技能。此外，MSTP，AB/GYN部和部门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，参加学术会议的资金，有机会结识杰出人士病毒学，免疫学和ob/gyn领域，以及支持性和协作的研究环境。 Van Ert女士将完成她的MSTP培训，并在OB/Gyn购买研究住所胎儿医学奖学金，并最终在学术医学中心任职研究plapeta内母亲界界面处的宿主 - 病原体免疫反应。