Hepatitis B virus X protein localizes to mitochondria and regulates apoptosis in primary rat hepatocytes

2021 ◽  
Author(s):  
Amy J. Clippinger
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Rat Hepatocytes ◽  
X Protein ◽  
Primary Rat Hepatocytes ◽  
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.

scholarly journals Hepatitis B Virus X Protein and Simian Virus 5 V Protein Exhibit Similar UV-DDB1 Binding Properties To Mediate Distinct Activities

2003 ◽  
Vol 77 (11) ◽  
pp. 6274-6283 ◽  
Author(s):  
Olivier Leupin ◽  
Séverine Bontron ◽  
Michel Strubin
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Simian Virus ◽  
Binding Activity ◽  
X Protein ◽  
Binding Properties ◽  
V Protein ◽  
Dna Binding Activity ◽  
Simian Virus 5 ◽  
B Virus

ABSTRACT The UV-damaged DNA-binding activity protein (UV-DDB) consists of two subunits, DDB1 and DDB2, and functions in DNA repair and cell cycle regulation. The DDB1 subunit is a target for the hepatitis B virus X protein (HBx). Binding of HBx to DDB1 interferes with cell growth and viability in culture and has been implicated in the establishment of viral infection. DDB1 also interacts with the V proteins encoded by several paramyxoviruses including simian virus 5 (SV5), which prevent interferon signaling by targeting either STAT1 or STAT2 proteins for proteolysis. The role of V binding to DDB1, however, remains unclear. Here we show that the V protein of SV5 (SV5-V) and HBx exhibit strikingly similar DDB1 binding properties. Thus, SV5-V and HBx bind to DDB1 in a mutually exclusive manner, and SV5-V shares with HBx the ability to enhance the steady-state levels of DDB1 and to inhibit its association with DDB2. Yet only HBx induces cell death, and SV5-V can prevent HBx from doing so by blocking its interaction with DDB1. Binding of SV5-V to DDB1 may serve another function, since SV5-V shows a decreased ability to induce STAT1 degradation in cells expressing reduced amounts of DDB1. These findings demonstrate that HBx performs a unique function through its association with DDB1 for which SV5-V cannot substitute and suggest that SV5-V and HBx have evolved to bind DDB1 to achieve distinct functions, both by a mechanism that does not involve DDB2.

scholarly journals Hepatitis B virus X protein plays an important role in gastric ulcers

2012 ◽  
Vol 28 (5) ◽  
pp. 1653-1658 ◽  
Author(s):  
PENG-TAO GUO ◽  
DONG YANG ◽  
ZHE SUN ◽  
HUI-MIAN XU
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Gastric Ulcers ◽  
X Protein ◽  
B Virus
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