Inflammation and Therapy for Respiratory Virus Infection

正在进行的研究重点是探索对急性呼吸道病毒感染的病理炎症反应，并利用这些信息制定创造性的策略，以避免这种疾病的致命后遗症。 在2020财年，我们贡献了一(1)篇原始研究文稿： 手稿#1： 标题：一种自然小鼠模型揭示了系统性毛细血管渗漏综合征的遗传决定因素 (克拉克森病)。 全身性毛细血管渗漏综合征(SCLS，Clarkson病)是一种病因不明的疾病，其特征是反复发作的蛋白质和液体渗漏到周围组织，导致全身浮肿和低血压休克。SCLS的发病机制和遗传学基础仍不清楚。在这里，我们确定了一个近亲交配的小鼠品系SJL，它概括了SCLS的基本特征，包括对组胺和感染引发的血管泄漏的敏感性。我们将这一特征命名为组胺高敏感性(HHS/HHS)，并将其定位在6号染色体上。HHS与人类中与SCLS关联最强的基因组位点(3p25.3)同线，揭示了发生血管高通透性的易感性具有在人和小鼠之间保守的强大遗传成分，并为SCLS提供了一个自然发生的动物模型。对HHS的遗传分析可能揭示出同源候选基因，这些基因不仅对SCLS有贡献，而且对更广泛的血管屏障功能的正常和失调机制也有贡献。 我们的贡献：我们提供专业知识和试剂，帮助探索这些小鼠对急性呼吸道病毒感染的反应，急性呼吸道病毒感染是引发这种综合征血管渗漏的主要病理生理因素之一。 裁判：拉扎·A，谢正，陈EC，陈伟，斯科特·兰姆，罗宾·艾施，克雷门佐夫·迪恩，罗森博格，帕里克·SM，布兰肯霍恩EP，特舍尔·C，德雷·公里。2019年。共产主义生物。2：398。

Ongoing research focuses on the exploration of pathologic inflammatory responses to acute respiratory virus infection and the use of this information to develop creative strategies to circumvent the lethal sequelae characteristic of this disease. In Fiscal year (FY) 2020, we contributed to one (1) original research manuscript: Manuscript #1: Title: A natural mouse model reveals genetic determinants of systemic capillary leak syndrome (Clarkson disease). The systemic capillary leak syndrome (SCLS, Clarkson disease) is a disorder of unknown etiology characterized by recurrent episodes of vascular leakage of proteins and fluids into peripheral tissues, resulting in whole-body edema and hypotensive shock. The pathologic mechanisms and genetic basis for SCLS remain elusive. Here we identify an inbred mouse strain, SJL, which recapitulates cardinal features of SCLS, including susceptibility to histamine- and infection-triggered vascular leak. We named this trait "Histamine hypersensitivity" (Hhs/Hhs) and mapped it to Chromosome 6. Hhs is syntenic to the genomic locus most strongly associated with SCLS in humans (3p25.3), revealing that the predisposition to develop vascular hyperpermeability has a strong genetic component conserved between humans and mice and providing a naturally occurring animal model for SCLS. Genetic analysis of Hhs may reveal orthologous candidate genes that contribute not only to SCLS, but also to normal and dysregulated mechanisms underlying vascular barrier function more generally. Our contribution: We provided expertise and reagents that facilitated an exploration of the responses of these mice to an acute respiratory virus infection, one of the major pathophysiologic factors that incite vascular leak in this syndrome. Ref: Raza A, Xie Z, Chan EC, Chen WS, Scott LM, Robin Eisch A, Krementsov DN, Rosenberg HF, Parikh SM, Blankenhorn EP, Teuscher C, Druey KM. 2019. Commun Biol. 2:398.