Spread of Human Respiratory Syncytial virus is facilitated by virus-induced filopodia
Human respiratory syncytial virus (RSV) is a member of the Pneumoviridae family that is a well known cause of acute lower respiratory tract infections and hospitalisations in children. Despite its prevalence, there is currently no vaccine or effective drug that can prevent and tackle infections by this virus. Therefore, understanding the involvement of host factors in the exacerbation of infection is an important step towards preventing progression to more serious conditions, such as bronchiolitis.
Recently, Mehedi and colleagues conducted a genome-wide siRNA screen, which identified actin-related protein 2 (ARP2) as a host factor participating in RSV infection. Interestingly, knockdown of the expression of ARP2 had no effect on the initial entry process of the virus and did not cause any significant reductions in viral gene expression in the first 24 hours of the infection process. Following on from this, viral gene expression was reduced concurrent with an apparent inhibition of RSV spread to close by cells. At 72 hours, the extent of this effect was indicated by a 10-fold reduction in the release of infectious virus particles from the ARP-2 depleted host cells.
Further investigations demonstrated that RSV infection of human lung epithelial A549 cells enhances motility and induces the formation of filopodia in an ARP2-dependent manner. These filopodia are expected to have a critical role in viral spread by shuttling RSV into vulnerable nearby cells that are susceptible to infection. The authors also found that filopodia induction could be achieved by expression of RSV F protein from a plasmid in the absence of the other proteins that comprise the virus structure. Therefore, this study clearly links ARP2 and filopodia formation to host cell motility and spread of RSV.
Further research is required to determine if these results are a true representation of what occurs during RSV infection of the lower respiratory tract epithelial layer. If so, inhibition of actin polymerisation could be an effective way to hinder the spread of RSV infection and a future target for novel therapeutics.
Original Research Paper:Actin-Related Protein 2 (ARP2) and Virus-Induced Filopodia Facilitate Human Respiratory Syncytial Virus Spread. 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. Published: December 7, 2016. http://dx.doi.org/10.1371/journal.ppat.1006062
Image source: CDC/ Dr. Erskine Palmer – This media comes from the Centers for Disease Control and Prevention’s Public Health Image Library (PHIL), with identification number #276. https://commons.wikimedia.org/w/index.php?curid=2201186
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