Viral pathogenesis of chronic inflammatory lesions of the placenta

胎盘慢性炎症病变的病毒发病机制

• 批准号: 10463753
• 负责人: Linda M Ernst
• 金额: $ 56.68万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-06 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10463753
• 关键词: Acute; Affect; Antiviral Response; Area; Bacterial Infections; Biological; Biological Assay; Biological Markers; Birth; Blood; Blood specimen; Child Health; Chorion; Chronic; Clinical; Cytomegalovirus; Data; Detection; Development; Diagnostic tests; Etiology; Event; Fetal Growth Retardation; Future; Gene Expression; Gene Expression Profile; Gene Expression Regulation; Genomics; Growth; Herpesviridae; High-Throughput Nucleotide Sequencing; Immune response; Immunohistochemistry; Inflammation; Inflammatory; Inflammatory Response; Influenza A virus; Investigation; Lead; Lesion; Methods; Morbidity - disease rate; Neonatal; Nucleic Acids; Outcome; Pathway interactions; Patients; Placenta; Positioning Attribute; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Pregnant Women; Premature Birth; Process; Public Health; Reaction; Research; Resources; Risk; Sampling; Signal Transduction; T-Lymphocyte; Testing; Therapeutic; Therapeutic Intervention; Time; Tissues; Transcript; Umbilical Cord Blood; United States; Up-Regulation; Vasculitis; Vertebrate Viruses; Viral; Viral Genes; Viral Genome; Viral Pathogenesis; Virus; Virus Diseases; Woman; Work; adverse pregnancy outcome; amniotic cavity; biomarker development; cohort; cost; design; experimental study; improved; innovation; intraamniotic infection; mortality risk; pathogenic virus; perinatal health; predictive test; prevent; racial diversity; response; transcriptome sequencing; viral detection; virus identification

PROJECT SUMMARY Preterm birth and intrauterine growth restriction are significant public health problems in the United States, affecting 10% and 3-9% of births, respectively. These adverse pregnancy outcomes result in increased risk of mortality and lifelong morbidities, in addition to substantial monetary costs of >$26 billion annually. Intrauterine/placental inflammation contributes to more than half of preterm birth. Much of the research related to placental inflammation has focused on acute inflammatory processes, which are typically driven by bacterial infections in the amniotic cavity, and little is known about the triggers or mechanisms that initiate and sustain chronic placental inflammation (CPI). It is well known that some CPI is associated with viral infection, such as cytomegalovirus, but in most cases, the etiology of CPI remains unknown. We hypothesize that most CPI is a chronic inflammatory reaction to viral infection in the placenta. We will comprehensively analyze placental tissue from pregnant women to determine whether viruses and antiviral inflammatory profiles are associated with CPI. Furthermore, we will test maternal blood collected during pregnancy to determine whether we can identify a viral and/or host signal that will predict development of CPI. Lastly, we will test neonatal umbilical cord blood for the presence of viral infection or host signal consistent with that seen in the placenta or maternal blood. This study has the potential to lead to the development of a predictive or diagnostic test for CPI, and it will help us to understand how CPI is triggered and progresses so that we may ultimately be able to design a preventative or therapeutic treatment. Ultimately, our ability to predict and/or prevent CPI will improve pregnancy outcomes and child health.

项目概要 早产和宫内生长受限是美国的重大公共卫生问题， 分别影响 10% 和 3-9% 的新生儿。这些不良妊娠结局会导致妊娠风险增加 死亡率和终生发病率，此外还有每年超过 260 亿美元的巨额货币成本。 子宫内/胎盘炎症导致一半以上的早产。大部分研究相关 胎盘炎症主要集中于急性炎症过程，该过程通常由细菌驱动 羊膜腔感染，但对于引发和维持的触发因素或机制知之甚少 慢性胎盘炎症（CPI）。众所周知，有些CPI与病毒感染有关，例如 巨细胞病毒，但在大多数情况下，CPI 的病因仍不清楚。我们假设大多数 CPI 是 胎盘病毒感染引起的慢性炎症反应。我们将全面分析胎盘组织 来自孕妇的数据，以确定病毒和抗病毒炎症特征是否与 CPI 相关。 此外，我们将测试怀孕期间收集的母血，以确定是否可以识别病毒 和/或预测 CPI 发展的宿主信号。最后，我们将检测新生儿脐带血是否 是否存在与胎盘或母血中所见一致的病毒感染或宿主信号。这项研究 有潜力开发 CPI 预测或诊断测试，它将帮助我们 了解 CPI 是如何触发和发展的，以便我们最终能够设计出预防性或 治疗性治疗。最终，我们预测和/或预防 CPI 的能力将改善妊娠结局并 儿童健康。