scholarly journals Hepatitis B Virus X Protein Induces Cell Death by Causing Loss of Mitochondrial Membrane Potential

2003 ◽  
Vol 278 (24) ◽  
pp. 22071-22078 ◽  
Author(s):  
Yumiko Shirakata ◽  
Katsuro Koike
Keyword(s):  
Cell Death ◽  
Membrane Potential ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane ◽  
X Protein ◽  
B Virus

scholarly journals Hepatitis B Virus HBx Protein Localizes to Mitochondria in Primary Rat Hepatocytes and Modulates Mitochondrial Membrane Potential

2008 ◽  
Vol 82 (14) ◽  
pp. 6798-6811 ◽  
Author(s):  
Amy J. Clippinger ◽  
Michael J. Bouchard
Keyword(s):  
Membrane Potential ◽  
Hepatitis B Virus ◽  
Liver Cancer ◽  
Hepatitis B ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane ◽  
Rat Hepatocytes ◽  
Mitochondrial Localization ◽  
Primary Rat Hepatocytes ◽  
B Virus

ABSTRACT Over 350 million people are chronically infected with hepatitis B virus (HBV), and a significant number of chronically infected individuals develop primary liver cancer. HBV encodes seven viral proteins, including the nonstructural X (HBx) protein. The results of studies with immortalized or transformed cells and with HBx-transgenic mice demonstrated that HBx can interact with mitochondria. However, no studies with normal hepatocytes have characterized the precise mitochondrial localization of HBx or the effect of HBx on mitochondrial physiology. We have used cultured primary rat hepatocytes as a model system to characterize the mitochondrial localization of HBx and the effect of HBx expression on mitochondrial physiology. We now show that a fraction of HBx colocalizes with density-gradient-purified mitochondria and associates with the outer mitochondrial membrane. We also demonstrate that HBx regulates mitochondrial membrane potential in hepatocytes and that this function of HBx varies depending on the status of NF-κB activity. In primary rat hepatocytes, HBx activation of NF-κB prevented mitochondrial membrane depolarization; however, when NF-κB activity was inhibited, HBx induced membrane depolarization through modulation of the mitochondrial permeability transition pore. Collectively, these results define potential pathways through which HBx may act in order to modulate mitochondrial physiology, thereby altering many cellular activities and ultimately contributing to the development of HBV-associated liver cancer.

Blocking of G1/S transition and cell death in the regenerating liver of Hepatitis B virus X protein transgenic mice

2006 ◽  
Vol 340 (3) ◽  
pp. 916-928 ◽  
Author(s):  
Bo-Kuan Wu ◽  
Chao-Chin Li ◽  
Huei-Jane Chen ◽  
Junn-Liang Chang ◽  
King-Song Jeng ◽  
...  
Keyword(s):  
Cell Death ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Transgenic Mice ◽  
Regenerating Liver ◽  
X Protein ◽  
B Virus

scholarly journals A direct role for hepatitis B virus X protein in inducing mitochondrial membrane permeabilization

2018 ◽  
Vol 25 (4) ◽  
pp. 412-420 ◽  
Author(s):  
H-R. Lee ◽  
Y. Y. Cho ◽  
G. Y. Lee ◽  
D-g. You ◽  
Y. D. Yoo ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Mitochondrial Membrane ◽  
Membrane Permeabilization ◽  
X Protein ◽  
Direct Role ◽  
B Virus ◽  
Mitochondrial Membrane Permeabilization

scholarly journals Association of hepatitis B virus X protein with mitochondria causes mitochondrial aggregation at the nuclear periphery, leading to cell death

Oncogene ◽  
1999 ◽  
Vol 18 (50) ◽  
pp. 6965-6973 ◽  
Author(s):  
Shinako Takada ◽  
Yumiko Shirakata ◽  
Noriko Kaneniwa ◽  
Katsuro Koike
Keyword(s):  
Cell Death ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Nuclear Periphery ◽  
X Protein ◽  
B Virus

scholarly journals Hepatitis B Virus X Protein Stimulates Viral Genome Replication via a DDB1-Dependent Pathway Distinct from That Leading to Cell Death

2005 ◽  
Vol 79 (7) ◽  
pp. 4238-4245 ◽  
Author(s):  
Olivier Leupin ◽  
Séverine Bontron ◽  
Céline Schaeffer ◽  
Michel Strubin
Keyword(s):  
Cell Death ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Cell Viability ◽  
Viral Genome ◽  
Genome Replication ◽  
Mrna Levels ◽  
X Protein ◽  
Hbv Replication ◽  
B Virus

ABSTRACT The hepatitis B virus (HBV) X protein (HBx) is essential for virus infection and has been implicated in the development of liver cancer associated with chronic infection. HBx can interact with a number of cellular proteins, and in cell culture, it exhibits pleiotropic activities, among which is its ability to interfere with cell viability and stimulate HBV replication. Previous work has demonstrated that HBx affects cell viability by a mechanism that requires its binding to DDB1, a highly conserved protein implicated in DNA repair and cell cycle regulation. We now show that an interaction with DDB1 is also needed for HBx to stimulate HBV genome replication. Thus, HBx point mutants defective for DDB1 binding fail to complement the low level of replication of an HBx-deficient HBV genome when provided in trans, and one such mutant regains activity when directly fused to DDB1. Furthermore, DDB1 depletion by RNA interference specifically compromises replication of wild-type HBV, indicating that HBx produced from the viral genome also functions in a DDB1-dependent fashion. We also show that HBx in association with DDB1 acts in the nucleus and stimulates HBV replication mainly by enhancing viral mRNA levels, regardless of whether the protein is expressed from the HBV genome itself or supplied in trans. Interestingly, whereas HBx induces cell death in both HepG2 and Huh-7 hepatoma cell lines, it enhances HBV replication only in HepG2 cells, suggesting that the two activities involve distinct DDB1-dependent pathways.

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