A novel host factor for human respiratory syncytial virus

ABSTRACT

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.

KEYWORDS:

• ARP2
• A549 cells
• cell motility
• filopodia
• RSV
• virus cell-to-cell spread

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Disclosure of potential conflicts of interest

No potential conflicts of interest were disclosed.

Acknowledgments

We thank Dr. Margery Smelkinson, Biological Imaging Section, Research Technologies Branch, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH) for her help with STED macroscopy.

Funding

This study was supported by the Intramural Research Program of NIAID, NIH.