Pathology/Pathogenesis

Immunohistochemistry analysis has shown that viral antigens are distributed primarily within the endothelium of capillaries throughout various tissues from patients with HPS. Marked accumulations of hantaviral antigens are seen in the pulmonary microvasculature and in follicular dendritic cells within the lymphoid follicles of spleen and lymph nodes. Hantaviral nucleic acids can also be localized to endothelial and inflammatory cells in tissues from HPS cases by using in situ hybridization. Electron micrographic studies confirm the infection of endothelial cells and macrophages in the lungs of HPS patients. Typical hantaviral inclusions are seen frequently in pulmonary endothelial cells, and their identity can be confirmed by immunolabeling. In the heart, endothelial staining is mainly in the capillaries of the myocardium and varies from focal immunostaining in some cases to diffuse and extensive staining in others. Occasionally, staining of endothelial cells lining the endocardium is observed.

Functional impairment of vascular endothelium is central to the pathogenesis of HPS. However, the pathogenesis of HPS is complex, and a myocardial depressant may contribute significantly to the mortality of this disease. It is unclear how the shock syndrome relates to factors such as viral distribution and immunologic and pharmacological mediators of capillary permeability. There appears to be compartmentalization of a selective immune response in the lungs of HPS patients in combination with extremely high levels of viral antigens in the pulmonary vasculature. This feature suggests that the mechanism of inflammatory cell recruitment in the lungs of HPS patients may result from specific attraction and adherence of a selective population of inflammatory cells to an activated pulmonary microvascular endothelium.