Blocking intercellular adhesion molecule-1 on human epithelial cells decreases respiratory syncytial virus infection

The respiratory syncytial virus (RSV) causes potentially fatal lower respir atory tract infection in infants. The molecular mechanism of RSV infection is unknown. Our data show that RSV colocalizes with intercellular adhesion molecule-1 (ICAM-1) on the HEp-2 epithelial cell surface. Furthermore, a ne utralizing anti-ICAM-1 mAb significantly inhibits RSV infection and infecti on-induced secretion of proinflammatory chemokine RANTES and mediator ET-1 in HEp-2 cells. Similar decrease in RSV infection is also observed in A549, a type-a alveolar epithelial cell Line, and NHBE, the normal human bronchi al epithelial cell Line when pretreated with anti-ICAM-1 mAb prior to RSV i nfection. Incubation of virus with soluble ICAM-1 also significantly decrea ses RSV infection of epithelial cells. Binding studies using ELISA indicate that RSV binds to ICAM-1, which can be inhibited by an antibody to the fus ion F protein and also the recombinant F protein can bind to soluble ICAM-1 , suggesting that RSV interaction with ICAM-1 involves the F protein. It is thus concluded that ICAM-1 facilitates RSV entry and infection of human ep ithelial cells by binding to its F protein, which is important to viral rep lication and infection and may lend itself as a therapeutic target. (C) 200 1 Academic Press.