TRIGEMINAL NEUROBIOLOGY--REACTIVATION OF LATENT HSV-1

三叉神经生物学--潜伏 HSV-1 的重新激活

• 批准号: 3425754
• 负责人: FRANK J JENKINS
• 金额: $ 3.61万
• 依托单位: HENRY M. JACKSON FDN FOR THE ADV MIL/MED
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-05-01 至 1994-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3425754
• 关键词: Herpesviridae disease; Salmonella typhimurium; cornea; cyclophosphamide; cyclosporines; cytotoxic T lymphocyte; disease /disorder model; ganglions; general anesthesia; herpes simplex virus 1; immunoglobulins; immunosuppressive; interferon gamma; interleukin 1; interleukin 2; interleukin 6; laboratory mouse; latent virus infection; murine hepatitis virus; neurobiology; neurotropic virus; radiation dosage; relapse /recurrence; stressor; tissue /cell culture; transforming growth factors; trigeminal nerve; tumor necrosis factor alpha; ultraviolet radiation; virus infection mechanism; virus protein

Herpes simplex virus (HSV) infections consist of several distinct stages; namely a primary infection, a latent infection and a reactivation of latent virus producing recurrent disease. In HSV infections of the mouth (herpes labialis), the trigeminal ganglion serves as the site of latent infection. Since a large portion of the population is estimated to have latent HSV infections and since recurrent infections probably represent the largest reservoir of HSV, efforts to control viral reactivation and therefore recurrent infections are extremely important in controlling the spread of the virus in the population. The exact mechanism(s) of HSV latency and reactivation including the roles of the immune, nervous and endocrine systems are largely unknown. Studies designed to unravel the interactions and roles of these different systems in viral reactivation from within the trigeminal ganglia are required before effective intervention can be designed. The single most important tool needed to study HSV reactivation is a good animal model, which unfortunately, does not currently exist. The primary goal of this research proposal is to establish an animal model system for the reactivation of latent HSV-1 from the trigeminal ganglia of mice. Using a well established mouse corneal model for HSV latency, viral reactivation will be achieved using a variety of stressors including infection with mouse hepatitis virus or salmonella typhimurium; use of the immuno-suppressive drugs cyclophosphamide and cyclosporin A; general anesthesia; and exposure to sub-erythemal doses of ultra-violet irradiation. Viral reactivation will be detected by monitoring HSV- specific immunoglobulins, cytotoxic T-cell activity, isolation of infectious virus and the presence of HSV-specific proteins in mouse tissues. Using this model system, additional studies will be performed to analyze the role of immune T cells, and the cytokines interleukin-1 (IL1), IL2, IL6, tumor necrosis factor alpha (TNFalpha), interferon gamma (IFNgamma), and transformed growth factor beta (TGFbeta) in the reactivation of latent HSV-1 virus.

单纯疱疹病毒（HSV）感染包括几个不同的阶段; 即原发感染、潜伏感染和潜伏感染的再激活。 产生复发性疾病的病毒。 在口腔HSV感染（疱疹 唇肌），三叉神经节作为潜伏感染的部位。 由于估计大部分人群患有潜伏性HSV 感染，因为复发性感染可能是最大的 HSV的储库，努力控制病毒再活化，因此 复发性感染对控制 病毒在人群中。 HSV潜伏期的确切机制， 包括免疫、神经和内分泌的作用 系统基本上是未知的。 研究旨在揭示 以及这些不同的系统在病毒再激活中的作用。 三叉神经节需要有效的干预， 设计了 研究HSV再活化所需的最重要工具 是一个很好的动物模型，不幸的是，目前还不存在。 的 本研究的主要目的是建立一种动物模型， 从三叉神经节再激活潜伏HSV-1的系统 小鼠 使用HSV潜伏期的良好建立的小鼠角膜模型， 使用各种应激源将实现重新激活，包括 感染小鼠肝炎病毒或鼠伤寒沙门氏菌; 免疫抑制药物环磷酰胺和环孢菌素A;一般 麻醉;以及暴露于皮下剂量的紫外线 辐照 病毒再激活将通过监测HSV- 特异性免疫球蛋白，细胞毒性T细胞活性， 感染性病毒和HSV特异性蛋白在小鼠中的存在 组织中 使用该模型系统，将进行额外的研究， 分析免疫T细胞和细胞因子白细胞介素-1（IL-1）的作用， IL 2、IL 6、肿瘤坏死因子α（TNF α）、干扰素γ IFN-γ和转化生长因子β（TGF β）的表达。 潜伏的HSV-1病毒的再活化。