scholarly journals Daunorubicin, a topoisomerase II poison, suppresses viral production of hepatitis B virus by inducing cGAS-dependent innate immune response

2018 ◽  
Vol 504 (4) ◽  
pp. 672-678 ◽  
Author(s):  
Hirotaka Imai ◽  
Hiromichi Dansako ◽  
Youki Ueda ◽  
Shinya Satoh ◽  
Nobuyuki Kato
Keyword(s):  
Immune Response ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Innate Immune Response ◽  
Topoisomerase Ii ◽  
Innate Immune ◽  
Viral Production ◽  
B Virus

scholarly journals Hepatitis B Virus and DNA Stimulation Trigger a Rapid Innate Immune Response through NF-κB

2016 ◽  
Vol 197 (2) ◽  
pp. 630-643 ◽  
Author(s):  
Masato Yoneda ◽  
Jinhee Hyun ◽  
Silvia Jakubski ◽  
Satoru Saito ◽  
Atsushi Nakajima ◽  
...  
Keyword(s):  
Immune Response ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Innate Immune Response ◽  
Innate Immune ◽  
B Virus

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.

scholarly journals Re-evaluation of hepatitis B virus clinical phases by systems biology identifies unappreciated roles for the innate immune response and B cells

Hepatology ◽  
2015 ◽  
Vol 62 (1) ◽  
pp. 87-100 ◽  
Author(s):  
Thomas Vanwolleghem ◽  
Jun Hou ◽  
Gertine van Oord ◽  
Arno C. Andeweg ◽  
A.D.M.E. Osterhaus ◽  
...  
Keyword(s):  
Immune Response ◽  
Systems Biology ◽  
Hepatitis B Virus ◽  
B Cells ◽  
Hepatitis B ◽  
Innate Immune Response ◽  
Innate Immune ◽  
B Virus

scholarly journals Capsid Allosteric Modulators Enhance the Innate Immune Response in Hepatitis B Virus–Infected Hepatocytes During Interferon Administration

2021 ◽  
Author(s):  
Keisuke Fukutomi ◽  
Hayato Hikita ◽  
Kazuhiro Murai ◽  
Tasuku Nakabori ◽  
Akiyoshi Shimoda ◽  
...  
Keyword(s):  
Immune Response ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Innate Immune Response ◽  
Innate Immune ◽  
Allosteric Modulators ◽  
B Virus

scholarly journals Natural Killer T Cell Activation Inhibits Hepatitis B Virus Replication in Vivo

2000 ◽  
Vol 192 (7) ◽  
pp. 921-930 ◽  
Author(s):  
Kazuhiro Kakimi ◽  
Luca G. Guidotti ◽  
Yasuhiko Koezuka ◽  
Francis V. Chisari
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Transgenic Mice ◽  
Nkt Cells ◽  
Innate Immune ◽  
Hbv Replication ◽  
B Virus ◽  
Ifn Γ

We have previously reported that hepatitis B virus (HBV)–specific CD8+ cytotoxic T lymphocytes and CD4+ helper T lymphocytes can inhibit HBV replication in the liver of HBV transgenic mice by secreting interferon (IFN)-γ when they recognize viral antigen. To determine whether an activated innate immune system can also inhibit HBV replication, in this study we activated natural killer T (NKT) cells in the liver of HBV transgenic mice by a single injection of α-galactosylceramide (α-GalCer), a glycolipid antigen presented to Vα14+NK1.1+ T cells by the nonclassical major histocompatibility complex class I–like molecule CD1d. Within 24 h of α-GalCer injection, IFN-γ and IFN-α/β were detected in the liver of HBV transgenic mice and HBV replication was abolished. Both of these events were temporally associated with the rapid disappearance of NKT cells from the liver, presumably reflecting activation-induced cell death, and by the recruitment of activated NK cells into the organ. In addition, prior antibody-mediated depletion of CD4+ and CD8+ T cells from the mice did not diminish the ability of α-GalCer to trigger the disappearance of HBV from the liver, indicating that conventional T cells were not downstream mediators of this effect. Finally, the antiviral effect of α-GalCer was inhibited in mice that are genetically deficient for either IFN-γ or the IFN-α/β receptor, indicating that most of the antiviral activity of α-GalCer is mediated by these cytokines. Based on these results, we conclude that α-GalCer inhibits HBV replication by directly activating NKT cells and by secondarily activating NK cells to secrete antiviral cytokines in the liver. In view of these findings, we suggest that, if activated, the innate immune response, like the adaptive immune response, has the potential to control viral replication during natural HBV infection. In addition, the data suggest that therapeutic activation of NKT cells may represent a new strategy for the treatment of chronic HBV infection.

scholarly journals Hepatitis B virus genomic nucleic acid in the activation and maturation of bone marrow-derived dendritic cells

2021 ◽  
pp. 109-119
Author(s):  
Chean Ring Leong ◽  
Tsukasa Seya ◽  
Woei Yenn Tong ◽  
Wen-Nee Tan
Keyword(s):  
Bone Marrow ◽  
Immune Response ◽  
Hepatitis B Virus ◽  
Nucleic Acid ◽  
Hepatitis B ◽  
Genomic Dna ◽  
Innate Immune ◽  
Adaptive Immune ◽  
B Virus

Hepatitis B virus (HBV) is the etiological agent that causes a self-limiting or chronic infection in the hepatocytes of about 250 million people worldwide. The role of adaptive immune system during HBV infection has been well studied. However, the innate immune system's responses against HBV during the early stage of infection largely remain unclear. In this study, we found that HBV genomic DNA or Salmon Sperm DNA (SSD) was able to induce the innate immune response in the macrophages cell line RAW264.7 but not the hepatocyte cell line, HepG2, indicating that hepatocytes may lack of a functional DNA-sensing pathway and hence are unable to respond to the presence of foreign DNA in the cytosol with type 1 IFN response. Thus, we hypothesized that non-parenchymal cells like the Antigen Presenting Cells (APC) might be crucial in triggering the initial immune response to suppress the virus replication and link the innate and adaptive responses. Using bone marrow-derived DCs (BMDC) as a model, this study demonstrated that HBV genomic DNA is able to induce cytokines like TNF-alpha, IL-6, and IL-12p40 secretion. We also examined the activation and maturation of BMDCs when exposed to the HBV genomic DNA intracellularly and extracellularly. A significant shift of CD86+ and CD40+ cell populations was observed during extracellular exposure of BMDC to Poly I:C and HBV genomic DNA, indicating that TLRs may be vital in the uptake of the extracellular viral DNA to activate the BMDCs. Moreover, transfection of intracellular nucleic acid stimuli, including HBV genomic DNA as well induced BMDCs maturation. Our findings highlight the critical function of DCs in antiviral response as a potential connection between the innate and adaptive immune systems during HBV pathogenesis. Nevertheless, further study is required to determine the role of cytosol DNA sensing pathway in DCs during HBV infection.

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