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)感染通常没有症状或可能导致反复皮损 嘴巴周围，俗称“唇疱疹”。典型的由HSV-1引起的眼部疱疹 通过三叉神经节(TG)的原发感染或重新激活，可产生严重的后遗症，包括 永久性角膜疤痕和失明。疱疹间质角膜炎(HSK)是最常见的病因之一 发达国家的传染性失明，全世界产生了超过40,000个新的严重失明病例 每年都有视力障碍或失明。有趣的是，HSK的大部分组织损伤被认为是 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，免疫细胞渗透，以及 新生血管持续存在。眼部HSV-1感染是如何导致这种慢性炎症综合征的 很好理解。通过研究影响宿主免疫反应的细胞因素，我们将描绘出 以病毒感染开始，以慢性炎症和视力丧失结束的一连串事件。这 该提案代表了我们对细胞因素的研究的继续，这些细胞因素对HSK很重要，使用 小鼠模型。这里提出的研究将涉及PILRA和HVEM的免疫调节功能。 单纯疱疹病毒(HSV)角膜炎。通过调查PILRA和HVEM对HSK的贡献，我们将 更好地理解病毒与宿主的相互作用在缺乏复制的情况下持续存在的炎症性综合征 病毒，为HSK的治疗干预提供了依据。