Journal article
Eliminating hepatitis B by antagonizing cellular inhibitors of apoptosis
G Ebert, C Allison, S Preston, J Cooney, JG Toe, MD Stutz, S Ojaimi, N Baschuk, U Nachbur, J Torresi, J Silke, CG Begley, M Pellegrini
Proceedings of the National Academy of Sciences of the United States of America | Published : 2015
Abstract
We have shown that cellular inhibitor of apoptosis proteins (cIAPs) impair clearance of hepatitis B virus (HBV) infection by preventing TNF-mediated killing/death of infected cells. A key question, with profound therapeutic implications, is whether this finding can be translated to the development of drugs that promote elimination of infected cells. Drug inhibitors of cIAPs were developed as cancer therapeutics to promote TNF-mediated tumor killing. These drugs are also known as Smac mimetics, because they mimic the action of the endogenous protein Smac/Diablo that antagonizes cIAP function. Here, we show using an immunocompetent mouse model of chronic HBV infection that birinapant and other..
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Awarded by National Health and Medical Research Council
Funding Acknowledgements
We thank Stephen Condon, Peter Revill, and Stephen Locarnini for discussions. Pei-Jer Chen and Ding-Shinn Chen constructed the hepatitis B virus infection vector for hydrodynamic infection. Linda Earnest-Silveira, Danielle Colledge, Xin Li, and Nadia Warner provided laboratory support. This work was supported by Australian Research Council Future Fellowship Award (to U.N.) and Grant FT1301000166; National Health and Medical Research Council Australia Career Development Award 637350 and Grants 541902 (to J.S.), 1006592 (to M.P.), 1045549 (to M.P.), and 1065626 (to M.P.); the Victorian State Government Operational Infrastructure Support; and the Independent Research Institutes Infrastructure Support Scheme of the Australian Government National Health and Medical Research Council.