Cellular inhibitor of apoptosis proteins prevent clearance of hepatitis B virus

被引：79

作者：

Ebert, Gregor ^{[1
,2
]}

Preston, Simon ^{[1
,2
]}

Allison, Cody ^{[1
,2
]}

Cooney, James ^{[1
]}

Toe, Jesse G. ^{[1
,2
]}

Stutz, Michael D. ^{[1
]}

Ojaimi, Samar ^{[1
,2
]}

Scott, Hamish W. ^{[1
]}

Baschuk, Nikola ^{[3
]}

Nachbur, Ueli ^{[1
,2
]}

Torresi, Joseph ^{[4
,5
]}

Chin, Ruth

Colledge, Danielle ^{[6
]}

Lie, Xin ^{[6
]}

Warner, Nadia ^{[6
]}

Revill, Peter ^{[6
]}

Bowden, Scott ^{[6
]}

Silke, John ^{[1
,2
]}

Begley, C. Glenn ^{[7
]}

Pellegrini, Marc ^{[1
,2
]}

机构：

[1] Walter & Eliza Hall Inst Med Res, Div Infect & Immun & Cell Signaling & Cell Death, Parkville, Vic 3052, Australia

[2] Univ Melbourne, Dept Med Biol, Parkville, Vic 3010, Australia

[3] LaTrobe Inst Mol Sci, Fac Sci Technol & Engn, Sch Mol Sci, Dept Biochem, Bundoora, Vic 3086, Australia

[4] Univ Melbourne, Austin Hosp, Dept Infect Dis, Heidelberg, Vic 3084, Australia

[5] Univ Melbourne, Austin Hosp, Dept Med, Heidelberg, Vic 3084, Australia

[6] Peter Doherty Inst, Victorian Infect Dis Reference Lab, Div Mol Res & Dev, Melbourne, Vic 3000, Australia

[7] TetraLog Pharmaceut Corp Inc, Res & Dev Div, Malvern, PA 19355 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2015年 / 112卷 / 18期

基金：

英国医学研究理事会; 澳大利亚研究理事会;

关键词：

hepatitis B virus; cellular inhibitor of apoptosis proteins; cIAP1; cIAP2; TNF; T-CELLS; ALPHA; MICE; CIAP1; INFECTION; BLOCKADE; DISEASE;

D O I：

10.1073/pnas.1502390112

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

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.

引用

页码：5797 / 5802

页数：6

共 35 条

[1]

Defective TCR expression in transgenic mice constructed using cDNA-based α- and β-chain genes under the control of heterologous regulatory elements [J].