Cellular inhibitor of apoptosis proteins prevent clearance of hepatitis B virus

Ebert, G; Preston, S; Allison, C; Cooney, J; Toe, JG; Stutz, MD; Ojaimi, S; Scott, HW; Baschuk, N; Nachbur, U; Torresi, J; Chin, R; Colledge, D; Li, X; WARNER, N; Revill, P; Bowden, S; Silke, J; Begley, CG; Pellegrini, M

Author(s): Ebert, G; Preston, S; Allison, C; Cooney, J; Toe, JG; Stutz, MD; Ojaimi, S; Scott, HW; Baschuk, N; Nachbur, U; Torresi, J; Chin, R; Colledge, D; Li, X; WARNER, N; Revill, P; Bowden, S; Silke, J; Begley, CG; Pellegrini, M;
Details: Publication Year 2015-04-20,Volume 112,Issue #18,Page 5797-802
Journal Title: Proceedings of the National Academy of Sciences of the United States of America
Publication Type: Journal Article
Abstract: Hepatitis B virus (HBV) infection can result in a spectrum of outcomes from immune-mediated control to disease progression, cirrhosis, and liver cancer. The host molecular pathways that influence and contribute to these outcomes need to be defined. Using an immunocompetent mouse model of chronic HBV infection, we identified some of the host cellular and molecular factors that impact on infection outcomes. Here, we show that cellular inhibitor of apoptosis proteins (cIAPs) attenuate TNF signaling during hepatitis B infection, and they restrict the death of infected hepatocytes, thus allowing viral persistence. Animals with a liver-specific cIAP1 and total cIAP2 deficiency efficiently control HBV infection compared with WT mice. This phenotype was partly recapitulated in mice that were deficient in cIAP2 alone. These results indicate that antagonizing the function of cIAPs may promote the clearance of HBV infection.
Publisher: National Academy of Sciences
Research Division(s): Infection And Immunity; Cell Signalling And Cell Death
PubMed ID: 25902529
Link To PubMed Central Version: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4426461/
Publisher's Version: https://doi.org/10.1073/pnas.1502390112
Open Access at Publisher's Site: http://www.pnas.org/content/112/18/5797.long
NHMRC Grants: NHMRC/637350, NHMRC/541901, NHMRC/541902, NHMRC/1006592, NHMRC/1045549, NHMRC/1065626,
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2015-05-20 09:04:09

Last Modified: 2015-05-20 09:16:31