Actin-Related Protein 2 (ARP2) and Virus-Induced Filopodia Facilitate Human Respiratory Syncytial Virus Spread

• DOI: 10.1371/journal.ppat.1006062
• Publication Date: 2016-12-07T23:45:02Z
• Authors: Masfique Mehedi; Thomas McCarty; Scott E. Martin; Cyril Le Nouën; Eugen Buehler; Yu-Chi Chen; Margery Smelkinson; Sundar Ganesan; Elizabeth R. Fischer; Linda G. Brock; Bo Liang; Shirin Munir; Peter L. Collins; Ursula J. Buchholz
• Keywords: Filopodia

Human respiratory syncytial virus (RSV) is an enveloped RNA that the most important viral cause of acute pediatric lower tract illness worldwide, and lacks a vaccine or effective antiviral drug. The involvement host factors in RSV replicative cycle remains poorly characterized. A genome-wide siRNA screen human lung epithelial A549 cells identified actin-related protein 2 (ARP2) as factor involved infection. ARP2 knockdown did not reduce entry, markedly gene expression during first 24 hr infection, but decreased thereafter, effect appeared to be due inhibition spread neighboring cells. Consistent with reduced spread, there was 10-fold reduction release infectious progeny virions ARP2-depleted at 72 post-infection. In addition, we found infection induced filopodia formation increased cell motility this phenotype dependent. Filopodia shuttle nearby uninfected cells, facilitating spread. Expression F alone from plasmid heterologous vector filopodia, indicating new role for protein, driving induction Thus, study roles RSV-induced motility, production, cell-to-cell