LSUHSC COBRE:HERPESVIRUS US GLYCOPROTEINS IN SEVERE INFLAMMATORY DISEASE

LSUHSC COBRE：严重炎症性疾病中的疱疹病毒和糖蛋白

• 批准号: 7610515
• 负责人: PATRICK F SMITH
• 金额: $ 26.11万
• 依托单位: LOUISIANA STATE UNIV HSC SHREVEPORT
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-05-01 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7610515
• 关键词: Biological; Brain; Cells; Computer Retrieval of Information on Scientific Projects Database; Disease; Equidae; Equus caballus; Funding; Future; Generations; Genes; Glycoproteins; Grant; Herpesviridae; Immune system; Inbred CBA Mice; Inflammatory; Institution; Investigation; Lung; Lung diseases; Mediating; Molecular; Mus; Pathogenesis; Pathology; Recombinants; Research; Research Personnel; Resources; Respiratory syncytial virus; Simplexvirus; Source; Spinal; Tissues; United States National Institutes of Health; Viral; Virus Diseases; Work; abstracting; brain cell; chemokine; cytokine; insight; mouse model; mutant; nervous system disorder; pathogen; respiratory; response

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Abstract, Introduction, Specific Aims and Progress Activation of the immune system by virus infection such that immunopathological responses occur is a major factor in severe respiratory disease mediated by respiratory pathogens--Influenzavirus and respiratory syncytial virus. Our previous work indicated that severe respiratory disease mediated by equine herpesvirus type 1 (EHV), involves an immunopathological mechanism and that the mouse mimics the disease of the natural host. In Equidae, EHV also causes immunopathological responses in the brain and spinal tissue, resulting in neurological disease. Thus our hypothesis is that investigation of EHV molecular pathogenesis in the mouse model may give insights into how the immune system is activated by virus infection and which immunological responses subsequently mediate respiratory and/or neurological disease. Our approach has involved the generation and subsequent biological assessment in the CBA mouse of recombinant EHV (rEHV) that express or fail to express viral glycoproteins gp2, gI, and gE encoded by three genes of the unique short (Us) segment. Glycoprotein gp2 of 791 residues is unique to EHV and was shown to be essential for respiratory disease mediated by a cytokine/chemokine storm. Use of gp2 mutant EHV revealed the portion of gp2 essential for lung pathology, and studies on the mechanism of pathogenesis are ongoing. In contrast, gI and gE do not mediate lung pathology but are important for EHV neuroinvasion. Whether the expression of proinflammatory factors by resident brain cells and recruitment of inflammatory cells that mediate EHV neurological disease is also mediated solely by gp2 is an important question for future work.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 摘要、引言、具体目标和进展 病毒感染激活免疫系统，发生免疫病理反应，是呼吸道病原体流感病毒和呼吸道合胞病毒介导的严重呼吸道疾病的主要因素。 我们之前的工作表明，由马疱疹病毒 1 型 (EHV) 介导的严重呼吸道疾病涉及免疫病理学机制，并且小鼠模仿自然宿主的疾病。 在马科动物中，超高压病毒还会引起大脑和脊髓组织的免疫病理反应，导致神经系统疾病。 因此，我们的假设是，对小鼠模型中 EHV 分子发病机制的研究可能有助于了解病毒感染如何激活免疫系统，以及哪些免疫反应随后介导呼吸系统和/或神经系统疾病。 我们的方法涉及在 CBA 小鼠中重组 EHV (rEHV) 的生成和随后的生物学评估，该重组 EHV 表达或不表达由独特短 (Us) 片段的三个基因编码的病毒糖蛋白 gp2、gI 和 gE。 791 个残基的糖蛋白 gp2 是 EHV 所特有的，并且被证明对于细胞因子/趋化因子风暴介导的呼吸道疾病至关重要。 gp2突变体EHV的使用揭示了gp2对于肺部病理学至关重要的部分，并且关于发病机制的研究正在进行中。 相比之下，gI 和 gE 不介导肺部病理，但对 EHV 神经侵袭很重要。 常驻脑细胞促炎因子的表达以及介导 EHV 神经系统疾病的炎症细胞的募集是否也仅由 gp2 介导，是未来工作的一个重要问题。