title: Role of vascular and lymphatic endothelial cells in hantavirus pulmonary syndrome suggests targeted therapeutic approaches.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Molecular Genetics and Microbiology, Stony Brook University , Stony Brook, New York.
authors.forename: Erich R
authors.initials: ER
authors.lastname: Mackow
authors.forename: Elena E
authors.initials: EE
authors.lastname: Gorbunova
authors.forename: Nadine A
authors.initials: NA
authors.lastname: Dalrymple
authors.forename: Irina N
authors.initials: IN
authors.lastname: Gavrilovskaya
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000627:therapeutic use; D002199:Capillary Permeability / Q000187:drug effects*; D006224:Cricetinae; D042783:Endothelial Cells / Q000378:metabolism / Q000502:physiology* / Q000821:virology; D000068876:Fingolimod Hydrochloride; D006476:Orthohantavirus / Q000502:physiology; D018804:Hantavirus Pulmonary Syndrome / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D054884:Host-Pathogen Interactions / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008647:Mesocricetus; D011409:Propylene Glycols / Q000627:therapeutic use; D011654:Pulmonary Edema / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D015398:Signal Transduction / Q000187:drug effects; D020123:Sirolimus / Q000627:therapeutic use; D013110:Sphingosine / Q000031:analogs & derivatives / Q000627:therapeutic use; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism
chemical_list: D000906:Antibodies; D007166:Immunosuppressive Agents; D011409:Propylene Glycols; D040301:Vascular Endothelial Growth Factor Receptor-2; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine; D020123:Sirolimus
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