scholarly journals Hepatitis B virus S gene therapy with 10-23 DNAzyme delivered by chitosan-g-stearic acid micelles

RSC Advances ◽  
2019 ◽  
Vol 9 (27) ◽  
pp. 15196-15204 ◽  
Author(s):  
Yun Hong ◽  
Dongsen Mao ◽  
Rui Wu ◽  
Zhe Gao ◽  
Tingting Meng ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Therapy ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Stearic Acid ◽  
Viral Gene ◽  
Important Research ◽  
S Gene ◽  
B Virus ◽  
Promising Application

DrzBS, which targets HBV S gene expression, has important research significance and potential application value. CSO-SA is a safe and efficient non-viral gene carrier and CSO-SA/DrzBS micelles are a promising application for anti-HBV gene therapy.

scholarly journals Interaction between STAT-3 and HNF-3 Leads to the Activation of Liver-Specific Hepatitis B Virus Enhancer 1 Function

2002 ◽  
Vol 76 (6) ◽  
pp. 2721-2729 ◽  
Author(s):  
Gulam Waris ◽  
Aleem Siddiqui
Keyword(s):  
Gene Expression ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Transcriptional Control ◽  
Viral Gene Expression ◽  
Cooperative Interaction ◽  
Viral Gene ◽  
Mobility Shift ◽  
B Virus ◽  
Stimulation Of

ABSTRACT The signal transducer and activator of transcription 3 (STAT-3), a member of the STAT family of proteins, binds to a large number of transcriptional control elements and regulates gene expression in response to cytokines. While it binds to its cognate nucleotide sequences, it has been recently shown to directly interact with other transcriptional factors in the absence of DNA. We report here one such novel interaction between STAT-3 and hepatocyte nuclear factor 3 (HNF-3) in the absence of DNA. We have identified a STAT-3 binding site within the core domain of hepatitis B virus (HBV) enhancer 1. The HBV enhancer 1 DNA-STAT-3 protein interaction is shown to be stimulated by interleukin-6 (IL-6) and epidermal growth factor, which leads to an overall stimulation of HBV enhancer 1 function and viral gene expression. Using mobility shift assays and transient transfection schemes, we demonstrate a cooperative interaction between HNF-3 and STAT-3 in mediating the cytokine-mediated HBV enhancer function. Cytokine stimulation of HBV gene expression represents an important regulatory scheme of direct relevance to liver disease pathogenesis associated with HBV infection.

Intracellular Inhibition of Hepatitis B Virus S Gene Expression by Chimeric DNA-RNA Phosphorothioate Minimized Ribozyme

2002 ◽  
Vol 12 (4) ◽  
pp. 257-264 ◽  
Author(s):  
Theresa May Chin Tan ◽  
Lei Zhou ◽  
Sandrine Houssais ◽  
Bee Leng Seet ◽  
Stephan Jaenicke ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
S Gene ◽  
B Virus ◽  
Intracellular Inhibition

scholarly journals Viral DNA-Dependent Induction of Innate Immune Response to Hepatitis B Virus in Immortalized Mouse Hepatocytes

2015 ◽  
Vol 90 (1) ◽  
pp. 486-496 ◽  
Author(s):  
Xiuji Cui ◽  
Daniel N. Clark ◽  
Kuancheng Liu ◽  
Xiao-Dong Xu ◽  
Ju-Tao Guo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Innate Immune Response ◽  
Viral Gene Expression ◽  
Innate Immune ◽  
Viral Gene ◽  
Viral Dna ◽  
B Virus

ABSTRACTHepatitis B virus (HBV) infects hundreds of millions of people worldwide and causes acute and chronic hepatitis, cirrhosis, and hepatocellular carcinoma. HBV is an enveloped virus with a relaxed circular (RC) DNA genome. In the nuclei of infected human hepatocytes, conversion of RC DNA from the incoming virion or cytoplasmic mature nucleocapsid (NC) to the covalently closed circular (CCC) DNA, which serves as the template for producing all viral transcripts, is essential to establish and sustain viral replication. A prerequisite for CCC DNA formation is the uncoating (disassembly) of NCs to expose their RC DNA content for conversion to CCC DNA. We report here that in an immortalized mouse hepatocyte cell line, AML12HBV10, in which RC DNA exposure is enhanced, the exposed viral DNA could trigger an innate immune response that was able to modulate viral gene expression and replication. When viral gene expression and replication were low, the innate response initially stimulated these processes but subsequently acted to shut off viral gene expression and replication after they reached peak levels. Inhibition of viral DNA synthesis or cellular DNA sensing and innate immune signaling diminished the innate response. These results indicate that HBV DNA, when exposed in the host cell cytoplasm, can function to trigger an innate immune response that, in turn, modulates viral gene expression and replication.IMPORTANCEChronic infection by hepatitis B virus (HBV) afflicts hundreds of millions worldwide and is sustained by the episomal covalently closed circular (CCC) DNA in the nuclei of infected hepatocytes. Release of viral genomic DNA from cytoplasmic nucleocapsids (NCs) (NC disassembly or uncoating) is a prerequisite for its conversion to CCC DNA, which can also potentially expose the viral DNA to host DNA sensors and trigger an innate immune response. We have found that in an immortalized mouse hepatocyte cell line in which efficient CCC DNA formation was associated with enhanced exposure of nucleocapsid-associated DNA, the exposed viral DNA indeed triggered host cytoplasmic DNA sensing and an innate immune response that was able to modulate HBV gene expression and replication. Thus, HBV can, under select conditions, be recognized by the host innate immune response through exposed viral DNA, which may be exploited therapeutically to clear viral persistence.

Antiviral therapy of hepatitis B virus infection: Blocking viral gene expression

1995 ◽  
Vol 17 (3) ◽  
pp. 321-331 ◽  
Author(s):  
Hubert E. Blum ◽  
Fritz von Weizsäcker ◽  
Stefan Wieland ◽  
Silke Offensperger ◽  
W.-B. Offensperger
Keyword(s):  
Gene Expression ◽  
Hepatitis B Virus ◽  
Virus Infection ◽  
Hepatitis B ◽  
Antiviral Therapy ◽  
Viral Gene Expression ◽  
Viral Gene ◽  
Hepatitis B Virus Infection ◽  
B Virus

scholarly journals Inhibition of Hepatitis B Virus Gene Expression and Replication by Hepatocyte Nuclear Factor 6

2015 ◽  
Vol 89 (8) ◽  
pp. 4345-4355 ◽  
Author(s):  
Ruidong Hao ◽  
Jing He ◽  
Xing Liu ◽  
Guozhen Gao ◽  
Dan Liu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hepatitis B Virus ◽  
Dna Replication ◽  
Hepatitis B ◽  
Viral Gene Expression ◽  
Viral Gene ◽  
Nuclear Factor ◽  
Hepatocyte Nuclear Factor ◽  
Gender Dimorphism ◽  
B Virus

ABSTRACTHepatitis B virus (HBV), a small enveloped DNA virus, chronically infects more than 350 million people worldwide and causes liver diseases from hepatitis to cirrhosis and liver cancer. Here, we report that hepatocyte nuclear factor 6 (HNF6), a liver-enriched transcription factor, can inhibit HBV gene expression and DNA replication. Overexpression of HNF6 inhibited, while knockdown of HNF6 expression enhanced, HBV gene expression and replication in hepatoma cells. Mechanistically, the SP2 promoter was inhibited by HNF6, which partly accounts for the inhibition on S mRNA. Detailed analysis showed that aciselement on the HBV genome (nucleotides [nt] 3009 to 3019) was responsible for the inhibition of the SP2 promoter by HNF6. Moreover, further analysis showed that HNF6 reduced viral pregenomic RNA (pgRNA) posttranscriptionally via accelerating the degradation of HBV pgRNA independent of La protein. Furthermore, by using truncated mutation experiments, we demonstrated that the N-terminal region of HNF6 was responsible for its inhibitory effects. Importantly, introduction of an HNF6 expression construct with the HBV genome into the mouse liver using hydrodynamic injection resulted in a significant reduction in viral gene expression and DNA replication. Overall, our data demonstrated that HNF6 is a novel host factor that can restrict HBV replication via both transcriptional and posttranscriptional mechanisms.IMPORTANCEHBV is a major human pathogen whose replication is regulated by host factors. Liver-enriched transcription factors are critical for many liver functions, including metabolism, development, and cell proliferation, and some of them have been shown to regulate HBV gene expression or replication in different manners. In this study, we showed that HNF6 could inhibit the gene expression and DNA replication of HBV via both transcriptional and posttranscriptional mechanisms. As HNF6 is differentially expressed in men and women, the current results may suggest a role of HNF6 in the gender dimorphism of HBV infection.

Inhibition on hepatitis B virus e-gene expression of 10–23 DNAzyme delivered by novel chitosan oligosaccharide–stearic acid micelles

2012 ◽  
Vol 87 (2) ◽  
pp. 1342-1347 ◽  
Author(s):  
Jing Miao ◽  
Xing-guo Zhang ◽  
Yun Hong ◽  
Yue-feng Rao ◽  
Qian Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Stearic Acid ◽  
Chitosan Oligosaccharide ◽  
E Gene ◽  
B Virus
Sign in / Sign up

Export Citation Format

Share Document