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 polymerase inhibits the interferon-inducible MyD88 promoter by blocking nuclear translocation of Stat1

2007 ◽  
Vol 88 (12) ◽  
pp. 3260-3269 ◽  
Author(s):  
Min Wu ◽  
Yang Xu ◽  
Shanshan Lin ◽  
Xiaonan Zhang ◽  
Li Xiang ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Nuclear Translocation ◽  
Antagonistic Activity ◽  
Binding Activity ◽  
Primary Response ◽  
Dependent Manner ◽  
Interferon Stimulated Genes ◽  
Dna Binding Activity ◽  
B Virus

Previous studies have suggested that hepatitis B virus (HBV) blocks expression of the alpha interferon (IFN-α)-inducible myeloid differential primary response protein (MyD88) gene. To study the molecular mechanism(s) of the inhibition of MyD88 expression by HBV, MyD88 promoter reporter plasmids and vectors expressing different HBV viral proteins were constructed. Co-transfection experiments showed that IFN-induced MyD88 promoter activity was inhibited by HBV polymerase expression in a dose-dependent manner and that the terminal protein (TP) domain of HBV polymerase was responsible for this antagonistic activity. Analysis of site mutants showed that the region targeted by the polymerase protein contained the signal transducer and activator of transcription (Stat) binding site. Chromatin immunoprecipitation analysis showed that the IFN-induced DNA-binding activity of Stat1 was affected. Further study demonstrated that the HBV polymerase protein inhibited the Stat1 nuclear translocation induced by IFN-α, but did not induce Stat1 degradation nor interfere with its phosphorylation. In addition, HBV polymerase could inhibit the transcriptional activity of other IFN-stimulated response element-driven promoters and the expression of interferon-stimulated genes (ISGs), such as Stat1 and ISG15. In summary, these results indicate that HBV polymerase is a general inhibitor of IFN signalling and can inhibit IFN-inducible MyD88 expression by inhibiting the activity of the MyD88 promoter through blocking the nuclear translocation of Stat1.

Multiple simian virus 40 enhancer elements mediate the trans-activating function of the X protein of hepatitis B virus

Virology ◽  
1991 ◽  
Vol 184 (2) ◽  
pp. 808-813 ◽  
Author(s):  
Birgit Luber ◽  
Elisabeth Bürgelt ◽  
Catherine Fromental ◽  
Masamoto Kanno ◽  
Werner Koch
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Simian Virus 40 ◽  
Simian Virus ◽  
X Protein ◽  
Activating Function ◽  
B Virus

scholarly journals Induction of the DNA-binding activity of c-jun/c-fos heterodimers by the hepatitis B virus transactivator pX.

1994 ◽  
Vol 14 (2) ◽  
pp. 989-998 ◽  
Author(s):  
G Natoli ◽  
M L Avantaggiati ◽  
P Chirillo ◽  
A Costanzo ◽  
M Artini ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Hepatitis B Virus ◽  
Protein Kinase ◽  
Dna Binding ◽  
Hepatitis B ◽  
Cell Lines ◽  
Binding Activity ◽  
Dna Binding Activity ◽  
Kinase C ◽  
B Virus

The hepatitis B virus (HBV) X protein (pX) is capable of activating transcription regulated by viral and cellular promoters containing binding sites for different transcription factors, including AP1. In this study we have analyzed the mechanisms of AP1 induction by pX. The hepatitis B virus transactivator was able to activate TRE (12-O-tetradecanoylphorbol-13-acetate response element)-directed transcription in different cell lines, including HepG2, HeLa, CV1, and PLC/PRF/5 cells. pX-induced AP1 activation in HepG2 cells was associated with an increase in the DNA-binding activity of c-Jun/c-Fos heterodimers, which was not dependent either on an increase in the overall amount of c-Fos and c-Jun proteins in the cells or on formation of dimers between pX and the two proteins, thus suggesting the involvement of posttranslational modifications of the transcription factor. The observation that the overexpression of c-Jun and c-Fos in the cells results in a strong augmentation of the effect of pX on TRE-directed transcription is additional evidence indicating the involvement of posttranscriptional modifications of c-Jun/c-Fos heterodimers. The increased AP1 binding observed in the presence of pX was unaffected by the protein kinase C inhibitors calphostin C and sphingosine and by the protein kinase A inhibitor HA1004, while it was almost completely blocked by staurosporine, a potent and nonspecific protein kinase inhibitor, suggesting that protein kinase C- and A-independent phosphorylation events might play a role in the phenomenon. The ability of pX also to increase TRE-directed transcription in cell lines in which AP1-binding activity is not increased (i.e., HeLa, CV1, and PLC/PRF/5 cells) suggests that pX can activate canonical TRE sites by different mechanisms as well.

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