Inflammation and Therapy for Respiratory Virus Infection

正在进行的研究重点是探索急性呼吸道病毒感染的病理性炎症反应，并利用这些信息制定创造性策略，以规避这种疾病的致命后遗症特征。

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.