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Signal cell seqencing of primary HCMV infections

原发性 HCMV 感染的信号细胞测序

基本信息

批准号：
10218861
负责人：
TIMOTHY F KOWALIK
金额：
$ 25.13万
依托单位：
UNIV OF MASSACHUSETTS MED SCH WORCESTER
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-03-01 至 2023-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10218861
关键词：
3-Dimensional Acquired Immunodeficiency Syndrome Acute Adolescent Antigens Antiviral Agents Biological Models Breast Feeding Cell Differentiation process Cell physiology Cells Cessation of life Congenital Abnormality Cytomegalovirus Cytomegalovirus Infections Development Discipline of Nursing Disease Epithelial Cells Event Fetus Fibroblasts Ganciclovir Gene Expression Genetic Hematopoietic stem cells Herpesviridae Human Human Milk Immune Immune response Immunologic Deficiency Syndromes In Vitro Individual Infection Innate Immune Response Intervention Knowledge Lactation Mediating Methodology Morbidity - disease rate Mothers Nursing infant Opportunistic Infections Oral Oral cavity Organ Patients Plasma Pregnant Women Primary Infection Protocols documentation Risk Sensorineural Hearing Loss Severe Combined Immunodeficiency Signal Transduction Solid Source Spontaneous abortion Swab Technology Teratogens Testing Tissue Model Tissues Transplant Recipients Umbilical Cord Blood Transplantation Vaccines Vertical Disease Transmission Viral Genes Virus Virus Replication Virus Shedding Woman acquired immunodeficiency cell type clinically relevant congenital infection data analysis pipeline fetus at risk improved in utero in vivo infection rate influenza infection insight mortality novel oral cavity epithelium oral infection pathogen prevent response single cell sequencing single-cell RNA sequencing three dimensional cell culture tool transcriptome transmission process viral resistance

项目摘要

Human cytomegalovirus (HCMV) is a herpesvirus commonly found in humans. HCMV infections are lifelong and usually do not have an apparent burden on the host. In individuals with natural or acquired immunodeficiency, HCMV can be a significant cause of disease and even death. HCMV is also the leading infectious cause of birth defects. How the virus infects a new host (primary infection) is poorly understood, especially in transmissions that occur during nursing. Lactating women who are positive for HCMV—which, globally, represents most women—shed virus in breast milk. About 4 in 10 women with HCMV will transmit the virus to their nursing infant. How this transmission occurs and the identity of cells in the oral cavity that become infected are poorly understood. Here we adapt cutting edge single cell RNA sequencing technology to identify which cells are infected in the oral cavity of nursing infants and determine the consequences of this infection on an individual cell basis. This approach allows us to propose a hypothesis that HCMV preferentially infects subsets of epithelial cells during oral primary infections that impact replication and host innate responses. We will test this hypothesis across two aims. The first, will adapt the single cell RNA sequencing technology to HCMV infected cultures of 3D oral epithelia tissues. The second aim will apply the technology to analyze primary infections in the oral cavity of nursing infants. These novel studies will provide new knowledge into HCMV primary infections and inform the development of improved interventions that prevent HCMV transmission.

人巨细胞病毒（HCMV）是一种常见于人类的疱疹病毒。HCMV感染是终身的，通常对宿主没有明显的负担。在具有自然或获得性免疫缺陷的个体中，HCMV可能是疾病甚至死亡的重要原因。HCMV也是导致出生缺陷的主要传染病。病毒如何感染新宿主（原发感染）尚不清楚，特别是在护理期间发生的传播。hcmv阳性的哺乳期妇女- - -在全球范围内代表了大多数妇女- - -在母乳中传播病毒。大约每10名携带HCMV的妇女中就有4人会将病毒传染给正在哺乳的婴儿。这种传播是如何发生的，以及口腔中被感染的细胞的身份，人们知之甚少。在这里，我们采用尖端的单细胞RNA测序技术来识别哺乳婴儿口腔中感染的细胞，并在单个细胞的基础上确定这种感染的后果。这种方法允许我们提出一个假设，即HCMV在口腔原发性感染期间优先感染上皮细胞亚群，从而影响复制和宿主先天反应。我们将从两个方面来检验这一假设。首先，将单细胞RNA测序技术应用于HCMV感染的3D口腔上皮组织培养。第二个目标将应用该技术来分析哺乳婴儿口腔的原发性感染。这些新颖的研究将提供关于HCMV原发性感染的新知识，并为开发预防HCMV传播的改进干预措施提供信息。