Receptor Usage and Regulation of the Immune Response in HSV Infection

HSV 感染中受体的使用和免疫反应的调节

基本信息

批准号：
10738934
负责人：
Richard M Longnecker
金额：
$ 23.5万
依托单位：
NORTHWESTERN UNIVERSITY AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-08-16 至 2025-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10738934
关键词：
Antibodies Biological Assay Blindness Brain Cell Surface Receptors Cell surface Cells Chronic Clinical Cornea Data Developed Countries Development Disease Disease Progression Event Experimental Designs Eye Eye Infections Flow Cytometry Foundations Glycoproteins Herpes Labialis Herpes Simplex Infections Herpes encephalitis Herpes stromal keratitis Herpetic Keratitis Human Image Immune Immune System Diseases Immune response Immunofluorescence Immunologic Immunoglobulins Immunomodulators Immunotherapy Infection Infiltration Inflammation Inflammatory Investigation Knock-out Knockout Mice Lesion Letters Ligands Lytic Macrophage Mediating Mediator Microglia Modeling Mus Neurons Oral cavity PVRL1 Pathogenesis Patients Phenotype Primary Infection Proteins Publications Publishing Recurrence Research Role Sampling Signal Transduction Simplexvirus Skin Structure of trigeminal ganglion Swab Symptoms Syndrome System Therapeutic Therapeutic Intervention Tissues Viral Virus Virus Diseases Virus Replication Visual impairment Visualization cell type chemokine clinically relevant corneal epithelium corneal scar cross reactivity cytokine detection platform genital herpes granulocyte imaging system immune activator immune cell infiltrate immune system function immunoregulation in vivo in vivo Model innovation insight liquid crystal polymer monocyte mouse model multiplex assay neovascularization novel novel therapeutics pathology imaging public health relevance receptor spectrograph targeted treatment time use

项目摘要

Project Description: Herpes simplex virus type I (HSV-1) infection is often asymptomatic or may produce recurrent lesions in and around the mouth, commonly called “cold sores.” Ocular herpetic disease, typically caused by HSV-1 either through primary infection or reactivation from the trigeminal ganglia (TG), can have serious sequelae, including permanent corneal scarring and blindness. Herpes stromal keratitis (HSK) is one of the most common causes of infectious blindness in the developed world, and worldwide produces over 40,000 new cases of severe vision impairment or blindness each year. Interestingly, the majority of HSK tissue damage is thought to be immune-mediated rather than resulting from direct lytic effects of the virus. Even after the virus has successfully been cleared, high levels of inflammatory cytokines and chemokines, immune cell infiltrates, and neovascularization persist. How HSV-1 infection of the eye leads to this chronic inflammatory syndrome is not well understood. By studying cellular factors that influence the host immune response, we will delineate the cascade of events that begin with a viral infection and end with chronic inflammation and vision loss. This proposal represents a continuation of our studies examining cellular factors that are important for HSK using a murine model. The studies proposed here will address the immunomodulatory functions of PILRA and HVEM in Herpes Simplex Virus (HSV) Keratitis. By investigating how PILRA and HVEM contributes to HSK, we will better understand the viral-host interactions inflammatory syndrome that persists in the absence of replicating virus, providing a basis for therapeutic interventions for HSK.

项目描述：单纯疱疹病毒I型（HSV-1）感染通常是不对称的，或者可能在在嘴周围，通常称为“唇疱疹”。眼疱疹疾病，通常是由HSV-1引起的通过三叉神经节（TG）的原发性感染或重新激活，可以具有严重的后遗症，包括永久的角膜疤痕和失明。疱疹基质角膜炎（HSK）是最常见的原因之一发达国家的传染失明，全球产生了40,000多个新案例视力障碍或失明。有趣的是，大多数HSK组织损害被认为是免疫介导的，而不是由病毒的直接裂解作用产生。即使病毒有成功清除，高水平的炎性细胞因子和趋化因子，免疫球浸润和新生血管造成持续存在。眼睛的HSV-1感染如何导致这种慢性炎症综合征不是理解。通过研究影响宿主免疫反应的细胞因素，我们将描述一系列以病毒感染开头的事件，并以慢性感染和视力丧失结束。这提案代表了我们研究的延续，研究了使用A的细胞因素对HSK很重要鼠模型。此处提出的研究将解决PILRA和HVEM的免疫调节功能在单纯疱疹病毒（HSV）角膜炎中。通过调查Pilra和HVEM如何为HSK做出贡献，我们将更好地了解在没有复制的情况下持续存在的病毒宿主相互作用炎症综合征病毒，为HSK提供治疗干预措施的基础。