Newly emerged hantaviruses replicate primarily in the pulmonary endothelium, cause acute platelet loss, and result in hantavirus pulmonary syndrome (HPS). We now report that specific integrins expressed on platelets and endothelial cells permit the cellular entry of HPS-associated hantaviruses. Infection with HPS-associated hantaviruses, NY-1 and Sin Nombre virus (SNV), is inhibited by antibodies to ␤ 3 integrins and by the ␤ 3 -integrin ligand, vitronectin. In contrast, infection with the nonpathogenic (no associated human disease) Prospect Hill virus was inhibited by fibronectin and ␤ 1 -specific antibodies but not by ␤ 3 -specific antibodies or vitronectin. Transfection with recombinant ␣ IIb ␤ 3 or ␣ v ␤ 3 integrins rendered cells permissive to NY-1 and SNV but not Prospect Hill virus infection, indicating that ␣ IIb ␤ 3 and ␣ v ␤ 3 integrins mediate the entry of NY-1 and SNV hantaviruses. Furthermore, entry is divalent cation independent, not blocked by arginine-glycine-aspartic acid peptides and still mediated by, ligand-binding defective, ␣ IIb ␤ 3 -integrin mutants. Hence, NY-1 and SNV entry is independent of ␤ 3 integrin binding to physiologic ligands. These findings implicate integrins as cellular receptors for hantaviruses and indicate that hantavirus pathogenicity correlates with integrin usage.

Cell surface receptors for echovirus, a common human pathogen, were identified with monoclonal antibodies that protected susceptible cells from infection with echovirus 1. These monoclonal antibodies, which prevented virus attachment to specific receptor sites, recognized the alpha and beta subunits of the integrin VLA-2 (alpha 2 beta 1), a receptor for collagen and laminin. RD rhabdomyosarcoma cells expressed little VLA-2, did not bind to 35S-labeled virus, and resisted infection until transfected with complementary DNA encoding the alpha 2 subunit of VLA-2. Thus, integrins, adhesion receptors important in interactions between cells and with the extracellular matrix, can mediate virus attachment and infection.

Unique receptor sites for poliovirus are considered to be the primary determinant of the virus' cell and tissue-type specificity. To study the poliovirus-cell interaction, eight monoclonal antibodies that specifically block the cytopathic effects of poliovirus were generated by using HeLa cell preparations as immunogen and a newly developed colorimetric screening assay. Plaque-inhibition assays confirmed the viral specificity of the antibodies, and when one antibody,