Grant: Doctoral Award - Frederick Banting and Charles Best Canada Graduate Scholarships

Since their introduction almost thirty years ago, HIV-specific antiretroviral drugs (ART) have had a dramatic impact on AIDS related morbidity and mortality. However, long-term use has been linked to adverse effects, including accelerated aging and neurological dysfunction. Most importantly, ART represents a treatment and not a cure for HIV infection. Complete eradication of HIV in the body is prevented by the establishment of HIV latency, during which the virus remains in a dormant state within an infected cell. These cells form a stable HIV reservoir, which is unresponsive to current therapies and a likely source of infectious virus following treatment interruption. Therefore, the development of novel therapeutic approaches designed to eradicate the HIV reservoir is required. Human cells possess natural antiviral mechanisms that serve to prevent viral infection and replication. This response, however, is largely impaired during HIV infection by the virus itself, thereby promoting viral spread. While this impairment has been well studied during productive infection, it remains poorly described during latency. The outlined project therefore serves to characterize potential HIV-mediated impairment of the antiviral response within cells that form the latent HIV reservoir. In cancer research, similar impediments within antiviral signaling pathways have been exploited to generate new therapies. For example, a class of virus typically known to infect livestock has been found to specifically target and kill cancer cells that have defects in these antiviral pathways. The capacity of these viruses, termed oncolytic viruses (OV), to specifically target and destroy latently HIV-infected cells will form a second aim of study. If found to preferentially target latently infected cells, the use of OV as a potential therapeutic approach may provide a means by which to eradicate the HIV reservoir in a targeted fashion, thus significantly enhancing the management of HIV infection.