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能在以下部位产生复发性病变： 口腔周围，通常称为“唇疱疹”。眼部疱疹病，通常由 HSV-1 引起 通过原发感染或三叉神经节 (TG) 重新激活，可能会产生严重的后遗症，包括 永久性角膜疤痕和失明。疱疹性基质角膜炎 (HSK) 是最常见的原因之一 发达国家传染性失明的病例数超过 40,000 例 每年都有视力障碍或失明。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。即使在病毒出现之后 成功清除，高水平的炎症细胞因子和趋化因子，免疫细胞浸润， 新生血管持续存在。 HSV-1 眼睛感染如何导致这种慢性炎症综合征尚不清楚 很好理解。通过研究影响宿主免疫反应的细胞因素，我们将描述 以病毒感染开始并以慢性炎症和视力丧失结束的一系列事件。这 该提案代表了我们研究的延续，使用以下方法检查对 HSK 重要的细胞因素： 小鼠模型。这里提出的研究将解决 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 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 的治疗干预提供基础。