sirolimus and Hantavirus-Pulmonary-Syndrome

Hantaviruses in the Americas cause a highly lethal acute pulmonary edema termed hantavirus pulmonary syndrome (HPS). Hantaviruses nonlytically infect microvascular and lymphatic endothelial cells and cause dramatic changes in barrier functions without disrupting the endothelium. Hantaviruses cause changes in the function of infected endothelial cells that normally regulate fluid barrier functions. The endothelium of arteries, veins, and lymphatic vessels are unique and central to the function of vast pulmonary capillary beds that regulate pulmonary fluid accumulation.. We have found that HPS-causing hantaviruses alter vascular barrier functions of microvascular and lymphatic endothelial cells by altering receptor and signaling pathway responses that serve to permit fluid tissue influx and clear tissue edema. Infection of the endothelium provides several mechanisms for hantaviruses to cause acute pulmonary edema, as well as potential therapeutic targets for reducing the severity of HPS disease.. Here we discuss interactions of HPS-causing hantaviruses with the endothelium, roles for unique lymphatic endothelial responses in HPS, and therapeutic targeting of the endothelium as a means of reducing the severity of HPS disease.

Topics: Animals; Antibodies; Capillary Permeability; Cricetinae; Endothelial Cells; Fingolimod Hydrochloride; Hantavirus Pulmonary Syndrome; Host-Pathogen Interactions; Humans; Immunosuppressive Agents; Mesocricetus; Orthohantavirus; Propylene Glycols; Pulmonary Edema; Signal Transduction; Sirolimus; Sphingosine; Vascular Endothelial Growth Factor Receptor-2