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: 6718382
• 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 2006-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6718382
• 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严重的感染。 人类常见的复发性健康问题，尤其是免疫抑制 个人。原发感染解决后，出现潜伏状态 一直持续到死亡。紫外线等环境刺激会导致周期性 疾病复发。研究人员最近开发出了一种强大的 受刺激的 HSV 上皮细胞疾病再激活的小鼠模型 最小的紫外线照射。这非常类似于人类的 HSV 上皮疾病， 允许在相关实验中研究皮肤 HSV-1 再激活 系统。本申请中提出的研究将使用该模型来测试 重新激活 HSV-1 疾病是由于局部细胞破坏所致的假设 细胞因子平衡和疾病解决需要局部皮肤免疫学 变化。他们提议研究 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 TH1/TH2 平衡，从而诱导 HSV 重新激活。缺少 CD4 耗尽的动物中 CD4 反应的减少会导致严重且长期的 疾病。他们提出调节包括 IL-12 在内的局部免疫因子 和 IFN-γ 改变再激活过程以及成分的差异 局部免疫系统的功能会影响 HSV-1 感染的易感性。研究 将在免疫能力强的小鼠和 CD4 耗尽的小鼠中进行，产生 以与 HIV 中人类 HSV 疾病非常相似的方式重新激活 HSV 疾病 被感染的主机。具体来说，他们将表征免疫反应 HSV-1 在局部皮肤水平并定义相互作用的背景 皮肤 HSV-1 疾病再激活期间的细胞因子和免疫细胞； 确定浸润 T 淋巴细胞在原代细胞和再激活细胞中的作用 正常模型与免疫受损模型中的疾病；并确定功效 基因组疫苗候选物可预防原发感染和 疾病再激活的减弱。