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

• 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
• 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

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）感染通常无症状，或可在和 在口腔周围，通常被称为“唇疱疹”。眼疱疹病，通常由HSV-1引起， 通过原发性感染或三叉神经节（TG）的再激活，可能有严重的后遗症，包括 永久性角膜疤痕和失明。疱疹性角膜基质炎（HSK）是最常见的原因之一 发达国家的传染性失明，全世界产生了超过40，000例新的严重失明病例。 视力受损或失明。有趣的是，大多数HSK组织损伤被认为是 免疫介导的，而不是由病毒的直接裂解作用引起的。即使病毒已经 成功清除，高水平的炎性细胞因子和趋化因子，免疫细胞浸润， 新生血管持续存在。眼睛的HSV-1感染如何导致这种慢性炎症综合征， 很好理解。通过研究影响宿主免疫反应的细胞因子，我们将描述 开始于病毒感染，结束于慢性炎症和视力丧失的一连串事件。这 该建议代表了我们研究的继续，研究细胞因素对HSK的重要性， 小鼠模型。本研究将探讨PILRA和HVEM的免疫调节功能 单纯疱疹病毒（HSV）角膜炎。通过研究PILRA和HVEM对HSK的贡献，我们将 更好地了解病毒-宿主相互作用炎症综合征，在没有复制的情况下持续存在 病毒，为HSK的治疗干预提供依据。