Reactivated HSV-1 disease in immune compromised hosts

免疫受损宿主中重新激活的 HSV-1 疾病

• 批准号: 6858773
• 负责人: Diane E Goade
• 金额: $ 30万
• 依托单位: UNIVERSITY OF NEW MEXICO
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-04-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6858773
• 关键词: Herpesviridae vaccine; T lymphocyte; cytokine; disease /disorder model; disease /disorder prevention /control; drug screening /evaluation; epithelium; gene environment interaction; gene expression; genetically modified animals; herpes simplex virus 1; host organism interaction; immunodeficiency; immunomodulators; immunopathology; laboratory mouse; latent virus infection; nonhuman therapy evaluation; radiobiology; relapse /recurrence; skin disorder chemotherapy; skin infection; skin pharmacology; ultraviolet radiation; virus infection mechanism

DESCRIPTION: (Provided by the Applicant) Herpes virus infection is a very common recurrent health problem in humans, especially immuno suppressed individuals. After resolution of primary infection, a state of latency develops that persists until death. Environmental stimuli such as UV lead to periodic recrudescence of disease. The investigators have recently developed a powerful murine model of reactivated HSV disease of epithelium that is stimulated by a minimum UV exposure. This very closely mimics HSV epithelium disease in man, permitting study of cutaneous HSV-1 reactivation in a relevant experimental system. The studies proposed in this application will use this model to test the hypothesis that reactivated HSV-1 disease is due to a disruption in local cytokine balance, and disease resolution requires local cutaneous immunologic changes. They propose to study the immunopathology of HSV disease reactivation and suggest new treatments and vaccine strategies. They hypothesize that UV exposure results in secretion of soluble factors by keratinocytes that ultimately alter the TH1/TH2 balance which induces HSV from reactivation. Lack of CD4 responses in CD4 depleted animals then permit severe and prolonged disease. They propose that modulation of local immune factors including IL-12 and IFN-gamma alter the reactivation process and that differences of components of the local immune systems impact susceptibility to HSV-1 infection. Studies will be done in immune competent mice and in mice depleted of CD4 which yields reactivated HSV disease in a manner very similar to human HSV disease in HIV infected hosts. Specifically, they will characterize the immune response to HSV-1 at the local cutaneous level and to define the context of interplay of cytokines and immune cells during reactivated cutaneous HSV-1 disease; determine the role of infiltrating T lymphocytes in primary and reactivated disease in normal versus immune compromised models; and determine efficacy of genomic vaccine candidates in prevention of primary infection and in attenuation of reactivated disease.

描述：(申请人提供)疱疹病毒感染是一种非常 人类常见的复发性健康问题，尤其是免疫抑制 个人。在原发感染消失后，会出现潜伏期 这种情况会一直持续到死亡。紫外线等环境刺激会导致周期性 疾病的复发。调查人员最近开发了一种强大的 A刺激小鼠上皮型单纯疱疹病毒病模型的建立 最低紫外线暴露量。这非常接近于人类单纯疱疹病毒上皮病， 皮肤HSV-1再激活的相关实验研究 系统。本申请中提出的研究将使用此模型来测试 重新激活HSV-1疾病的假说是由于局部 细胞因子平衡和疾病解决需要局部皮肤免疫 改变。他们建议研究HSV疾病重新激活的免疫病理学 并提出新的治疗方法和疫苗策略。他们假设紫外线 暴露导致角质形成细胞分泌可溶性因子， 最终改变导致HSV重新激活的TH1/TH2平衡。缺欠 在CD_4耗尽的动物中的CD_4反应允许严重和持续的 疾病。他们认为，包括IL-12在内的局部免疫因子的调节 和干扰素-γ改变再激活过程和成分的差异 影响当地免疫系统对HSV-1感染的易感性。研究 将在免疫能力强的小鼠和CD4耗尽的小鼠身上进行，这会产生 在HIV中重新激活HSV疾病的方式与人类HSV疾病非常相似 受感染的宿主。具体地说，他们将描述免疫反应的特点 HSV-1在局部皮肤水平，并定义相互作用的背景 细胞因子和免疫细胞在重新激活的皮肤HSV-1疾病中； 确定浸润性T淋巴细胞在原发和再活化中的作用 在正常和免疫受损模型中的疾病；并确定 候选基因组疫苗在预防原发感染和艾滋病中的应用 再发疾病的减退。