The Role of Reactive Oxygen Species in Herpesvirus Infection

Photodynamic Inc. (PDI) is a world leader in light-activated anti-microbial technologies that work bygenerating reactive oxygen species (ROS). The company has identified an opportunity to dramatically expandits product offerings with innovative anti-viral technologies. Infection with herpes simplex virus-1 (HSV-1) isvery common, with most individuals infected in early childhood. Initial infection of skin cells is often followedby the establishment of a dormant form of infection known as 'latency' in long-lived cells of the nervoussystem. Periodic reactivation from latency permits re-infection of skin cells near the site of initial infection,which facilitates virus spread. Latency is what allows herpesviruses to establish life-long infection.Viral infection of animal cells triggers antiviral responses. ROS can directly damage viral components andshape antiviral responses by modifying cellular antiviral proteins. It is clear that ROS play a major role inantiviral defence, both at the level of the individual cells, and in whole animals, but detailed understanding ofmolecular mechanisms is lacking.The primary objective of this collaborative project is to advance fundamental understanding of how ROSaffects cellular proteins that dictate responses to HSV-1 infection. PDI will provide proprietary plant extractsfor the project, along with light sources required to stimulate ROS production. Light-activated plant extractsand other sources of ROS will be administered to herpesvirus-infected cells, followed by measurement ofchanges in the composition of cellular antiviral proteins, and measurement of effects on virus replication.This collaboration represents a unique opportunity to generate new basic knowledge about how ROS shapesantiviral responses. A successful project will lead to future mechanistic studies and afford PDI the opportunityto make anti-viral research a core competency.