Modeling Filovirus Infection of and Trafficking through Skin

模拟丝状病毒通过皮肤的感染和贩运

基本信息

批准号：
9751755
负责人：
Wendy Jean Maury
金额：
$ 76.74万
依托单位：
UNIVERSITY OF IOWA
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-08-01 至 2022-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9751755
关键词：
Acute Africa Animal Model Animals Antigen-Presenting Cells Antiviral Therapy Apical Autopsy Bathing Biological Cell Surface Receptors Cells Dermal Dermis Disease Outbreaks Ebola virus Epidemic Epidermis Event Family Fibroblasts Filoviridae Infections Filovirus Human Individual Infection Infectious Skin Diseases Interruption Lesion Macaca Measures Mediating Modality Modeling Mus Palliative Care Pathway interactions Patients Petechiae Population Predisposition Production Property Public Health Reporting Research Route Sampling Satellite Viruses Skin Source Supporting Cell Surface Testing Therapeutic Time Vaccines Viral Antigens Viral Load result Viral load measurement Viremia Virion Virus Virus Diseases cell type human tissue improved in vivo inhibitor/antagonist keratinization keratinocyte mortality nonhuman primate pathogen public health priorities receptor success trafficking transmission process uptake viral transmission

项目摘要

Abstract: Filoviruses such as Ebola virus (EBOV) are found on the skin's surface at late times of infection when viremia is high. Evidence indicates that skin-associated virus is an important source of virus transmitted to others. Yet, how virus arrives at the surface is not well understood. Our preliminary studies suggest that EBOV can traffic to the surface of the skin by infecting both dermal and epidermal cell populations within the skin and that this route of virus delivery to the skin's surface is important in vivo. Yet, which cells within the skin support filovirus replication and are principally responsible for virus load are unknown. Here, we seek to understand EBOV interactions with skin as it egresses from the body. We will also evaluate if EBOV is able to enter through the intact or abraded skin surface. We hypothesize that direct infection of cells within the skin serves as an important route of EBOV transmission. To examine this, we will test the following aims. Purified primary skin cells (e.g. keratinocytes, fibroblasts, and antigen presenting cells) will be examined for their support of EBOV infection and we will determine if these same populations are infected in skin explants. Further, we will determine if known cell surface receptors are expressed in permissive skin cells and explants and if inhibition of virus interactions with those receptors blocks EBOV infection. We will also assess the timing of skin involvement in EBOV infection in vivo in mice and in macaques. At the completion of these important studies, an understanding of EBOV interactions with skin will be developed and a new model platform will be established for studying filovirus infections of highly relevant human tissue.

抽象的：在感染后期，在皮肤表面上发现了诸如埃博拉病毒（EBOV）之类的丝病毒当病毒血症高。证据表明皮肤相关病毒是病毒传播给他人。然而，病毒如何到达表面尚不清楚。我们的初步研究表明，EBOV可以通过感染两个皮肤中的皮肤和表皮细胞群体，这种病毒递送到皮肤的表面在体内很重要。但是，哪些细胞在皮肤中支持丝状病毒复制并且主要负责病毒负荷是未知的。在这里，我们试图了解Ebov 与皮肤相互作用时，它会从体内流出。我们还将评估Ebov是否能够通过完整或磨损的皮肤表面输入。我们假设细胞的直接感染皮肤内是EBOV传播的重要途径。为了检查一下，我们将测试以下目标。纯化的原代皮肤细胞（例如角质形成细胞，成纤维细胞和抗原呈现细胞）将检查其对EBOV感染的支持，我们将确定是否确定这些相同的种群在皮肤外植体中被感染。此外，我们将确定是否已知细胞表面受体在允许的皮肤细胞和外植体中表达，以及病毒的抑制与这些受体的相互作用阻碍了EBOV感染。我们还将评估皮肤的时间参与小鼠和猕猴的体内EBOV感染。完成这些重要的研究，将了解EBOV与皮肤相互作用的理解，并有一个新的将建立模型平台来研究高度相关的人类的丝状病毒感染组织。