A novel host factor for human respiratory syncytial virus.

Human respiratory syncytial virus (RSV) is the leading viral cause of severe lower respiratory disease in young children worldwide. As part of a genome-wide siRNA screen, we recently discovered that actin-related protein 2 (ARP2) is a host factor in the RSV replication cycle. ARP2 is a major constituent of the ARP2/3 complex, which catalyzes actin polymerization involved in cell morphology and motility. In the course of investigating this finding, we also found that RSV infection of human lung epithelial A459 cells induced filopodia formation and stimulated cell motility. The increase in filopodia formation was due, at least in part, to the expression of the RSV fusion F protein. Filopodia formation and increased cell motility appeared to shuttle RSV particles to nearby uninfected cells, facilitating virus cell-to-cell spread. ARP2 depletion did not reduce RSV entry or gene expression early in infection, but reduced subsequent virus production, filopodia formation, cell motility, and viral spread. Thus, the RSV F protein, ARP2-mediated actin nucleation, filopodia formation, and cell mobility all contribute to previously unrecognized mechanisms for RSV cell-to-cell spread that may promote RSV pathogenesis.