Cellular inhibitor of apoptosis proteins prevent clearance of hepatitis B virus
Autor: | Gregor Ebert, Jesse G. Toe, Ruth Chin, C. Glenn Begley, Nadia Warner, Simon Preston, Xin Li, John Silke, Joseph Torresi, Peter Revill, Marc Pellegrini, James P Cooney, Samar Ojaimi, Michael D. Stutz, Cody C. Allison, Hamish W Scott, Danielle Colledge, Ueli Nachbur, Scott Bowden, Nikola Baschuk |
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Rok vydání: | 2015 |
Předmět: |
Hepatitis B virus
Cirrhosis Genotype CD8 Antigens Ubiquitin-Protein Ligases Biology medicine.disease_cause Inhibitor of apoptosis Immunophenotyping Inhibitor of Apoptosis Proteins Liver disease Interferon-gamma Mice medicine Animals Hepatitis Immunosuppression Therapy Multidisciplinary Tumor Necrosis Factor-alpha Liver Neoplasms Hepatitis B Biological Sciences medicine.disease Virology Baculoviral IAP Repeat-Containing 3 Protein 3. Good health Mice Inbred C57BL Disease Models Animal Phenotype Liver Immunology CD4 Antigens DNA Viral Hepatocytes Cytokines Tumor necrosis factor alpha Liver cancer Signal Transduction |
Zdroj: | Proceedings of the National Academy of Sciences of the United States of America |
DOI: | 10.1073/pnas.1502390112 |
Popis: | 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. |
Databáze: | OpenAIRE |
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