Subversion of autophagy by the Kaposi's sarcoma-associated herpesvirus

Our laboratory is dedicated to revealing the strategies that viruses employ to infect host tissues and establish chronic disease. In people suffering from AIDS, co-infection with the Kaposi's sarcoma-associated herpesvirus (KSHV, human herpesvirus-8) causes a tumour known as Kaposi's sarcoma (KS). It is not known precisely how KSHV causes tumour formation, but the emerging model is that different viral gene products collaborate to reprogram host cells and undermine host anti-viral and anti-cancer defences. Through our CIHR-funded research program, we seek to better understand how KSHV undermines a host defence known as autophagy. Autophagy is a recycling mechanism that engulfs and degrades cellular structures to liberate raw materials and energy. Virus structures can also be targeted by the autophagy machinery, thereby preventing virus replication and alerting the immune system. Thus, autophagy can be thought of as a form of anti-viral defence. Autophagy also plays an essential role in a host anti-cancer defence known as oncogene-induced senescence. Our recent studies have demonstrated that KSHV encodes a viral protein, v-FLIP, that facilitates bypass of oncogene-induced senescence, thereby allowing KSHV infected cells to proliferate and initiate cancer. We seek to better understand precisely how KSHV undermines autophagy at different stages of the viral replicative cycle, and determine the consequences for viral fitness and the fate of the infected host cells. The ultimate objective is to use this knowledge to develop new anti-viral therapies that prevent KS tumour formation.