Dr Greg Ebert - Walter and Eliza Hall Institute

Dr Greg Ebert - Walter and Eliza Hall Institute

Location: 
Davis Auditorium with linkup to Bundoora
Start Time: 
Wed, 11/03/2015 - 1:00pm
End Time: 
Wed, 11/03/2015 - 2:00pm

​Eliminating HBV infection by antagonizing cellular inhibitor of apoptosis proteins

Wednesday Seminar

Greg works as a senior postdoc in the lab of Marc Pellegrini in the division of Infection and Immunity since 2010. His research focuses on identifying host factors and mechanisms that attenuate or restrict the ability of hosts to eradicate chronic and overwhelming human infections such as hepatitis B. Hepatitis B virus (HBV) infection can result in a spectrum of outcomes from immune-mediated control to disease progression, such as liver cirrhosis and liver cancer. Liver cancer is the second most common cause of cancer related deaths in the world and in Australia it is the most rapidly increasing cause of cancer related deaths.

The host molecular pathways that influence and contribute to the different outcomes in HBV infected patients are not well known. Greg and colleagues recently identified that particular Inhibitor of Apoptosis Proteins (IAPs) restrict the ability of mice to eliminate HBV. Greg’s work has uncovered that certain of these IAPs attenuate tumor necrosis factor (TNF) signaling during hepatitis B infection and they prevent the death of infected hepatocytes thus allowing viral persistence. Moreover, administration of birinapant (TetraLogic Pharmaceuticals, USA), a clinical-stage IAP-antagonist induces preferential elimination of infected hepatocytes and clearance of infection. Current antiviral therapies do not eradicate HBV infection, but the addition of birinapant promoted the efficacy of nucleoside analogue viral polymerase inhibitors in eliminating virus. The study shows that birinapant, and possibly other cIAP antagonists, have efficacy in treating HBV infection and perhaps other intracellular infections. A phase I/IIa clinical trial of birinapant in HBV infected patients was commenced in November 2014.