Cellular entry of Hantaan virus A9 strain: Specific interactions with β3 integrins and a novel 70 kDa protein

Cellular entry of pathogenic hantaviruses had been shown to be mediated by β3 integrins. However, no direct evidence exists that hantavirus binds to β3 integrins, and integrin β3 subunit is not expressed on some cells permissive to hantavirus infection. In this report, utilizing β3-integrin-transfected CHO cells, we demonstrated that integrin β3 subunit renders CHO cells susceptible to Chinese Hantaan virus (HTN) strain A9 (isolated in China), and the viral infection was correspondingly inhibited by antibodies to αvβ3, αIIbβ3, β3, and αv integrins. Furthermore, virus overlay protein-binding assay and 'quarternary Western' analysis indicate that HTN A9 directly interacts with β3 integrins and an unidentified 70 kDa protein. These findings indicate that β3 integrins play a crucial role in cellular entry of HTN A9 via specific interactions with the virus. In addition, a novel 70 kDa protein may serves as a candidate receptor or alternative cellular component for interaction with HTN.