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.

scholarly journals IFI16 induces inflammation in Hepatitis B Virus-Associated Glomerulonephritis by Regulating the Caspase-1 /IL-1ß pathway

2021 ◽  
Author(s):  
Li Liu ◽  
Xiuhua Zhao ◽  
Shuangshuang Xie ◽  
Cheng Li ◽  
Yue Guo ◽  
...  
Keyword(s):  
Immune Response ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Cell Line ◽  
293T Cell ◽  
Hbv Infection ◽  
Caspase 1 ◽  
B Virus

Abstract Aims & backgroundIFI16 plays an important role in innate immunity against invasive microbial infection by sensing double-stranded DNA viruses due to caspase-1-dependent inflammasome activation and subsequent maturation and secretion of IL-1β. However, the role of IFI16 in regulating the immune response to viruses in Hepatitis B Virus-Associated Glomerulonephritis(HBV-GN), especially in sensing the hepatitis B virus (HBV), has not been determined. In this study,, we investigated the inflammatory role of IFI16 in HBV-GN.MethodsA total of 75 kidney tissues including 50 HBV-GN and 25 chronic glomerulonephritis (CCN) were collected to determine expression of IFI16, Caspase-1, and IL-1𝛽 by immunohistochemistry (IHC), and then the correlation between them was analyzed. In vitro, the overexpression or knockdown of IFI16 in regulating the immune response to HBV infection in the human glomerular mesangial (HGM) cell line and HEK-293T cell line. Quantitative Real-time PCR and western blotting were used to determine the expression of IFI16, Caspase-1 and IL-1β. The role effect of IFI16 in vivo was further investigated.ResultsIFI16 expression in HBV-GN biopsies (80.0%) was significantly higher than in CGN (24.0%) and was positively correlated with caspase-1 and IL-1𝛽 expression in HBV-GN. In vitro, over expression of IFI16 increased caspase-1 and IL-1𝛽 expression in HBV-infected HGM and HEK-293T cell lines, whereas knockdown of IFI16 mRNA by siRNA resulted in downregulation of the caspase-1 and IL-1𝛽 expression in both cell lines.ConclusionsThe elevation of IFI16 during HBV infection or replication may contribute to renal damage due to inflammation, thus providing a putative therapeutic target and a new avenue for studying the pathogenesis of HBV-GN.

scholarly journals Role of Immune Cells in Patients with Hepatitis B Virus-Related Hepatocellular Carcinoma

2021 ◽  
Vol 22 (15) ◽  
pp. 8011
Author(s):  
Hyo-Jung Cho ◽  
Jae-Youn Cheong
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cells ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Chronic Inflammation ◽  
Cd8 T Cells ◽  
Immune Cells ◽  
Adaptive Immune ◽  
B Virus

Hepatocellular carcinoma (HCC) develops almost entirely in the presence of chronic inflammation. Chronic hepatitis B virus (HBV) infection with recurrent immune-mediated liver damage ultimately leads to cirrhosis and HCC. It is widely accepted that HBV infection induces the dysfunction of the innate and adaptive immune responses that engage various immune cells. Natural killer (NK) cells are associated with early antiviral and antitumor properties. On the other hand, inflammatory cells release various cytokines and chemokines that may promote HCC tumorigenesis. Moreover, immunosuppressive cells such as regulatory T cells (Treg) and myeloid-derived suppressive cells play a critical role in hepatocarcinogenesis. HBV-specific CD8+ T cells have been identified as pivotal players in antiviral responses, whilst extremely activated CD8+ T cells induce enormous inflammatory responses, and chronic inflammation can facilitate hepatocarcinogenesis. Controlling and maintaining the balance in the immune system is an important aspect in the management of HBV-related HCC. We conducted a review of the current knowledge on the immunopathogenesis of HBV-induced inflammation and the role of such immune activation in the tumorigenesis of HCC based on the recent studies on innate and adaptive immune cell dysfunction in HBV-related HCC.

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

Role of the cell-mediated immune response in the pathogenesis of hepatitis B virus infection

1995 ◽  
Vol 121 (S1) ◽  
pp. S15-S15
Author(s):  
C. Ferrari ◽  
A. Penna ◽  
A. Bertoletti ◽  
A. Cavalli ◽  
G. Missale ◽  
...  
Keyword(s):  
Immune Response ◽  
Hepatitis B Virus ◽  
Virus Infection ◽  
Hepatitis B ◽  
Hepatitis B Virus Infection ◽  
Cell Mediated Immune Response ◽  
B Virus

scholarly journals THE MECHANISMS OF IMMUNE ESCAPE BY HEPATITIS B VIRUS

2017 ◽  
Vol 72 (6) ◽  
pp. 408-419 ◽  
Author(s):  
M. V. Sokolova ◽  
M. V. Konopleva ◽  
Т. A. Semenenko ◽  
V. G. Akimkin ◽  
A. V. Tutelyan ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Immune Escape ◽  
Adaptive Immune Response ◽  
Host Cells ◽  
Cell Functions ◽  
Adaptive Immune ◽  
B Virus

The high prevalence of the hepatitis B virus (HBV) in population occurs mainly due to numerous mechanisms formed in the process of the virus evolution, contributing to its survival under immunological pressure. The review presents the most complete systematization and classification of various HBV protective mechanisms basing on their influence on different parts of congenital and adaptive immune response. The analysis of literature data allows for the conclusion that two basic principles underlie the mechanisms: the strategy of the «stealth virus» (virus’s escape from recognition by the immune system) and strategy of immunosuppression. The stealth virus strategy is performed as follows: special strategy of the HBV replication which prevents the recognition by the receptors of congenital immune system; occurrence of the vaccine escape mutants; isolation of the virus in host cells and tissues providing its inaccessibility to T-cells along with hyperproduction of subviral particles as traps for specific antibodies. The core principle of the immunosuppression implemented in hepatitis B therapy is based on the phenomenon of the viral apoptotic mimicry. The result of this interaction strategy is dysfunction of NK and NKT-cells, inactivation of dendritic cell functions, and suppression of the adaptive immune response. The review demonstrates that interaction between HBV and the immune system of the macro organism is in some kind of «dynamic equilibrium» depending on numerous factors. Specific molecular targets of the viral impact are described. We propose to expand the research on the influence of the host’s genetic factors on the development of congenital and adaptive immune response against HBV, especially during the real infectious process which results in the improvement of approaches to the therapy by developing personalized treatment methods.

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