Pathogenesis of the hantavirus pulmonary syndrome

Hantavirus pulmonary syndrome caused by hantaviruses in the Americas presents as a broad clinical spectrum ranging from brief febrile prodrome with only thrombocytopenia to rapidly progressive fulminant pulmonary edema and shock. This vascular leak syndrome confined almost exclusively to the lung is initiated by the noncytolytic infection of capillary endothelial cells. A number of pathogenic mechanisms have been proposed, including immune cell-mediated injury, cytokine-mediated injury and enhanced VEGF responses from intercellular junctions resulting from highly specific virus-integrin interactions. This review examines evidence for each of these potential mechanisms, with relevant references to its sister syndrome, hemorrhagic fever with renal syndrome, in Eurasia. Any mechanism or combination of mechanisms must be able to explain the massive pulmonary capillary leak at the severe extreme of the spectrum, a disease manifestation without parallel in clinical medicine.