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Cellular inhibitor of apoptosis proteins prevent clearance of hepatitis B virus.
Ebert, Gregor; Preston, Simon; Allison, Cody; Cooney, James; Toe, Jesse G; Stutz, Michael D; Ojaimi, Samar; Scott, Hamish W; Baschuk, Nikola; Nachbur, Ueli; Torresi, Joseph; Chin, Ruth; Colledge, Danielle; Li, Xin; Warner, Nadia; Revill, Peter; Bowden, Scott; Silke, John; Begley, C Glenn; Pellegrini, Marc.
Afiliação
  • Ebert G; Division of Infection and Immunity and Cell Signaling and Cell Death, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, The University of Melbourne, Parkville, VIC 3010, Australia;
  • Preston S; Division of Infection and Immunity and Cell Signaling and Cell Death, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, The University of Melbourne, Parkville, VIC 3010, Australia;
  • Allison C; Division of Infection and Immunity and Cell Signaling and Cell Death, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, The University of Melbourne, Parkville, VIC 3010, Australia;
  • Cooney J; Division of Infection and Immunity and Cell Signaling and Cell Death, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia;
  • Toe JG; Division of Infection and Immunity and Cell Signaling and Cell Death, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, The University of Melbourne, Parkville, VIC 3010, Australia;
  • Stutz MD; Division of Infection and Immunity and Cell Signaling and Cell Death, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, The University of Melbourne, Parkville, VIC 3010, Australia;
  • Ojaimi S; Division of Infection and Immunity and Cell Signaling and Cell Death, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, The University of Melbourne, Parkville, VIC 3010, Australia;
  • Scott HW; Division of Infection and Immunity and Cell Signaling and Cell Death, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia;
  • Baschuk N; Faculty of Science Technology and Engineering, School of Molecular Sciences, Department of Biochemistry, LaTrobe Institute for Molecular Science, Bundoora, VIC 3086, Australia;
  • Nachbur U; Division of Infection and Immunity and Cell Signaling and Cell Death, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, The University of Melbourne, Parkville, VIC 3010, Australia;
  • Torresi J; Department of Infectious Diseases and Department of Medicine, Austin Hospital, The University of Melbourne, Heidelberg, VIC 3084, Australia;
  • Chin R; Department of Infectious Diseases and Department of Medicine, Austin Hospital, The University of Melbourne, Heidelberg, VIC 3084, Australia;
  • Colledge D; Division of Molecular Research and Development, Victorian Infectious Diseases Reference Laboratory, Peter Doherty Institute, Melbourne, VIC 3000, Australia; and.
  • Li X; Division of Molecular Research and Development, Victorian Infectious Diseases Reference Laboratory, Peter Doherty Institute, Melbourne, VIC 3000, Australia; and.
  • Warner N; Division of Molecular Research and Development, Victorian Infectious Diseases Reference Laboratory, Peter Doherty Institute, Melbourne, VIC 3000, Australia; and.
  • Revill P; Division of Molecular Research and Development, Victorian Infectious Diseases Reference Laboratory, Peter Doherty Institute, Melbourne, VIC 3000, Australia; and.
  • Bowden S; Division of Molecular Research and Development, Victorian Infectious Diseases Reference Laboratory, Peter Doherty Institute, Melbourne, VIC 3000, Australia; and.
  • Silke J; Division of Infection and Immunity and Cell Signaling and Cell Death, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, The University of Melbourne, Parkville, VIC 3010, Australia;
  • Begley CG; Research and Development Division, TetraLogic Pharmaceuticals Corporation, Inc., Malvern, PA 19355.
  • Pellegrini M; Division of Infection and Immunity and Cell Signaling and Cell Death, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, The University of Melbourne, Parkville, VIC 3010, Australia; pellegrini@wehi.edu.au.
Proc Natl Acad Sci U S A ; 112(18): 5797-802, 2015 May 05.
Article em En | MEDLINE | ID: mdl-25902529
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.
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Texto completo: 1 Coleções: 01-internacional Temas: Geral Base de dados: MEDLINE Assunto principal: Vírus da Hepatite B / Ubiquitina-Proteína Ligases / Proteínas Inibidoras de Apoptose / Hepatite B Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Proc Natl Acad Sci U S A Ano de publicação: 2015 Tipo de documento: Article
Texto completo
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Buscar no Google

Texto completo: 1 Coleções: 01-internacional Temas: Geral Base de dados: MEDLINE Assunto principal: Vírus da Hepatite B / Ubiquitina-Proteína Ligases / Proteínas Inibidoras de Apoptose / Hepatite B Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Proc Natl Acad Sci U S A Ano de publicação: 2015 Tipo de documento: Article