Cellular inhibitor of apoptosis proteins prevent clearance of hepatitis B virus

Gregor Ebert, Simon Peter Preston, Cody Allison, James Cooney, Jesse G. Toe, Michael D Stutz, Samar Ojaimi, Hamish W. Scott, Nikola Baschuk, Ueli Nachbur, Joseph Torresi, Ruth Chin, Danielle Colledge, Xin Li, Nadia Warner, Peter Revill, Scott Bowden, John Silke, C Glenn Begley, Marc Pellegrini

Research output: Contribution to journalArticleResearchpeer-review

73 Citations (Scopus)

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 immuno-competent 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.

Original languageEnglish
Pages (from-to)5797-5802
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume112
Issue number18
DOIs
Publication statusPublished - 5 May 2015
Externally publishedYes

Keywords

  • Cellular inhibitor of apoptosis proteins
  • cIAP1
  • cIAP2
  • Hepatitis B virus
  • TNF

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