Zaikun Xu, University of Alberta

Zaikun Xu1, Jumari Snyman1, Joaquin Lopez Orozco1, Alberto Felix-Lopez2, Leanne Bilawchuk2, OIivier Julien3,4, David Marchant2,4 and Tom C. Hobman1,2,4 1Department of Cell Biology, Faculty of Medicine and Dentistry, University of Alberta 2Department of Medical Microbiology & Immunology, Faculty of Medicine and Dentistry, University of Alberta 3Department of Biochemistry, Faculty of Medicine and Dentistry, University of Alberta 4Li Ka Shing Institute of Virology, Faculty of Medicine and Dentistry, University of Alberta

Fighting & Responding

Respiratory syncytial virus (RSV) is a human pathogen that causes an enormous burden on the global healthcare system through infection of neonates and older adults. Unfortunately, treatment options for infected individuals are very limited and thus there is an urgent need to develop small molecule antiviral therapies. To date, strategies that target RSV proteins have not resulted in any licensed drugs. An alternative approach is to develop compounds that target host cell pathways that modulate RSV infection. Peroxisomes are ubiquitous organelles that play important roles in the host antiviral response. Here, we observed that the NS2 protein of RSV inhibits peroxisome biogenesis using at least three different mechanisms which explains in part how this viral protein is so effective in dampening the innate immune response. Through sequestration of Emerin, VAPB and PMP70, all of which induce peroxisomes and limit RSV replication when overexpressed, NS2 reduces the cellular peroxisome pool and consequently the magnitude of the interferon response. As peroxisome abundance can be modulated by a variety of drugs, we assessed whether pharmacological induction of peroxisomes reduced RSV infection. We show that multiple peroxisome-inducing compounds significantly reduce RSV replication thus providing rationale for further exploration of this strategy as a means to control RSV infection.