Pathogenic hantaviruses selectively inhibit β 3 integrin directed endothelial cell migration

Pathogenic hantaviruses selectively inhibit β 3 integrin directed endothelial cell migration Hantaviruses cause two diseases of man, hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). Pathogenic and non-pathogenic hantaviruses use β 3 and β 1 integrins, respectively, to enter endothelial cells. β 3 integrins were recently reported to bind receptors that regulate vascular permeability suggesting that hantavirus β 3 integrin interactions may regulate endothelial cell function and contribute to viral pathogenesis. In this study we investigated the ability of pathogenic and non-pathogenic hantaviruses to regulate β 3 and β 1 integrin directed endothelial cell functions. We found that pathogenic NY-1, SNV, HTN, SEO and PUU viruses blocked endothelial cell migration on β 3 , but not β 1 , integrin ligands. Migration is similarly inhibited by antibodies to β 3 integrins which selectively block vitronectin directed endothelial cell migration. As a result, the ability of endothelial cells to migrate on integrin ligands was selectively inhibited by only pathogenic hantaviruses. Infection by NY-1 virus inhibited endothelial cell migration as early as 24–48 h post-infection. In contrast, non-pathogenic PH and TUL viruses had no effect on the ability of endothelial cells to migrate on either β 3 or β 1 integrin ligands from 1 to 5 days post-infection. These findings indicate that only hantaviruses which use β 3 integrins, and are associated with HPS and HFRS diseases, functionally dysregulate endothelial cell migration. These findings further demonstrate that hantaviruses regulate only β 3 integrin directed endothelial cell functions and have no effect on β 1 integrin functions. Since β 3 integrins are linked to changes in vascular permeability and the maintenance of vascular integrity, these findings suggest a means by which hantavirus usage and regulation of β 3 integrins may contribute to hantavirus pathogenesis. Archives of Virology Springer Journals

Pathogenic hantaviruses selectively inhibit β 3 integrin directed endothelial cell migration

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