scholarly journals Hypoxic gene expression in chronic hepatitis B infected patients is not observed in state-of-art in vitro and mouse infection models

2020 ◽  
Author(s):  
PJ Liu ◽  
JM Harris ◽  
E Marchi ◽  
V D’Arienzo ◽  
T Michler ◽  
...  
Keyword(s):  
Gene Expression ◽  
Chronic Hepatitis ◽  
Hepatitis B ◽  
Chronic Hepatitis B ◽  
De Novo ◽  
Regulatory Protein ◽  
Hbv Infection ◽  
Infection Models

ABSTRACTHepatitis B virus (HBV) is the leading cause of hepatocellular carcinoma (HCC) worldwide. The prolyl hydroxylase domain (PHD)-hypoxia inducible factor (HIF) pathway is a key mammalian oxygen sensing pathway and is frequently perturbed by pathological states including infection and inflammation. We discovered a significant upregulation of hypoxia regulated gene transcripts in patients with chronic hepatitis B (CHB) in the absence of liver cirrhosis. We used state-of-the-art in vitro and in vivo HBV infection models to evaluate a role for HBV infection and the viral regulatory protein HBx to drive HIF-signalling. HBx had no significant impact on HIF expression or associated transcriptional activity under normoxic or hypoxic conditions. Furthermore, we found no evidence of hypoxia gene expression in HBV de novo infection, HBV infected human liver chimeric mice or transgenic mice with integrated HBV genome. Collectively, our data show clear evidence of hypoxia gene induction in CHB that is not recapitulated in existing models for acute HBV infection, suggesting a role for inflammatory mediators in promoting hypoxia gene expression.

scholarly journals Hypoxic gene expression in chronic hepatitis B virus infected patients is not observed in state-of-the-art in vitro and mouse infection models

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Peter Jianrui Liu ◽  
James M. Harris ◽  
Emanuele Marchi ◽  
Valentina D’Arienzo ◽  
Thomas Michler ◽  
...  
Keyword(s):  
Gene Expression ◽  
Chronic Hepatitis ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Chronic Hepatitis B ◽  
State Of The Art ◽  
Hbv Infection ◽  
Infection Models ◽  
B Virus

Abstract Hepatitis B virus (HBV) is the leading cause of hepatocellular carcinoma (HCC) worldwide. The prolyl hydroxylase domain (PHD)-hypoxia inducible factor (HIF) pathway is a key mammalian oxygen sensing pathway and is frequently perturbed by pathological states including infection and inflammation. We discovered a significant upregulation of hypoxia regulated gene transcripts in patients with chronic hepatitis B (CHB) in the absence of liver cirrhosis. We used state-of-the-art in vitro and in vivo HBV infection models to evaluate a role for HBV infection and the viral regulatory protein HBx to drive HIF-signalling. HBx had no significant impact on HIF expression or associated transcriptional activity under normoxic or hypoxic conditions. Furthermore, we found no evidence of hypoxia gene expression in HBV de novo infection, HBV infected human liver chimeric mice or transgenic mice with integrated HBV genome. Collectively, our data show clear evidence of hypoxia gene induction in CHB that is not recapitulated in existing models for acute HBV infection, suggesting a role for inflammatory mediators in promoting hypoxia gene expression.

scholarly journals Author Correction: Hypoxic gene expression in chronic hepatitis B virus infected patients is not observed in state-of-the-art in vitro and mouse infection models

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Peter Jianrui Liu ◽  
James M. Harris ◽  
Emanuele Marchi ◽  
Valentina D’Arienzo ◽  
Thomas Michler ◽  
...  
Keyword(s):  
Gene Expression ◽  
Chronic Hepatitis ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Chronic Hepatitis B ◽  
State Of The Art ◽  
Infection Models ◽  
Chronic Hepatitis B Virus ◽  
B Virus

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

scholarly journals In Vivo Bioluminescence Imaging of HBV Replicating Hepatocytes Allows for the Monitoring of Anti-Viral Immunity

Viruses ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2273
Author(s):  
Katrin Manske ◽  
Annika Schneider ◽  
Chunkyu Ko ◽  
Percy A. Knolle ◽  
Katja Steiger ◽  
...  
Keyword(s):  
T Cells ◽  
Chronic Hepatitis ◽  
Hepatitis B ◽  
Chronic Hepatitis B ◽  
Cd8 T Cells ◽  
Recombinant Adenovirus ◽  
Hbv Infection ◽  
High Dose ◽  
Viral Immunity

Immunity against hepatitis B virus (HBV) infection is complex and not entirely understood so far, including the decisive factors leading to the development of chronic hepatitis B. This lack of a mechanistic understanding of HBV-specific immunity is also caused by a limited number of suitable animal models. Here, we describe the generation of a recombinant adenovirus expressing an HBV 1.3-overlength genome linked to luciferase (Ad-HBV-Luc) allowing for precise analysis of the quantity of infected hepatocytes. This enables sensitive and close-meshed monitoring of HBV-specific CD8 T cells and the onset of anti-viral immunity in mice. A high dose of Ad-HBV-Luc developed into chronic hepatitis B accompanied by dysfunctional CD8 T cells characterized by high expression of PD1 and TOX and low expression of KLRG1 and GzmB. In contrast, a low dose of Ad-HBV-Luc infection resulted in acute hepatitis with CD8 T cell-mediated elimination of HBV-replicating hepatocytes associated with elevated sALT levels and increased numbers of cytotoxic HBV-specific CD8 T cells. Thus, the infectious dose was a critical factor to induce either acute self-limited or chronic HBV infection in mice. Taken together, the new Ad-HBV-Luc vector will allow for highly sensitive and time-resolved analysis of HBV-specific immune responses during acute and chronic infection.

scholarly journals Antiviral Treatment with Alpha Interferon Up-Regulates CD14 on Liver Macrophages and Its Soluble Form in Patients with Chronic Hepatitis B

2005 ◽  
Vol 49 (2) ◽  
pp. 590-599 ◽  
Author(s):  
Patrizia Carotenuto ◽  
Debby van Riel ◽  
André Artsen ◽  
Sven Bruijns ◽  
Fons G. Uytdehaag ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis B ◽  
Chronic Hepatitis B ◽  
Antiviral Treatment ◽  
Biologically Active ◽  
Alpha Interferon ◽  
Regulatory Function ◽  
Soluble Form

ABSTRACT To investigate whether therapy with alpha interferon (IFN-α) induces changes in intrahepatic antigen-presenting cells (APCs), we obtained liver biopsy specimens before, during, and after therapy with IFN-α from chronic hepatitis B patients whose viral load had already been reduced by at least 8 weeks of treatment with lamivudine. HLA-DR, CD1a, and CD83 were not modified by the therapy. The intralobular expression of CD68 on Kupffer cells remained stable, denoting no changes in the number of resident macrophages during IFN-α treatment. In contrast, CD14 was weakly expressed in the absence of IFN-α and was significantly up-regulated during therapy. At the same time, the levels of soluble CD14 and interleukin-10 in plasma increased significantly. In vitro, monocytes maintained in the presence of IFN-α differentiated into macrophages or dendritic cells with higher levels of expression of CD14 than that for the control cultures. During therapy with IFN-α, T-cell infiltration in the portal spaces was reduced, mainly due to a significant decrease in the number of CD8+ T cells. These findings show that IFN-α is biologically active on APCs in vivo and in vitro and suggest that this newly described regulatory function, together with the already known inhibitory effects on lymphocytes, may cooperate to reduce inflammation and consequent tissue damage in patients with chronic viral hepatitis.

scholarly journals Estimation of cellular immune response by evaluation of some cytokines in immunopathogenesis of chronic hepatitis B and C pre- and post- treated Iraqi patients (in vivo and in vitro)

2009 ◽  
Vol 6 (3) ◽  
pp. 533-541
Author(s):  
Baghdad Science Journal
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis B ◽  
Chronic Hepatitis B ◽  
Healthy Control ◽  
Elisa Technique ◽  
The Mean ◽  
Hbs Ag ◽  
Cellular Immune

Two groups of chronic hepatitis B and C virus patients were divided into Pre-treated patients (25 CHB patients with positive HBs Ag for more than 6 months and 40 CHC patients), and post-treated patients [12 CHB patients (4, 6, and 2 were treated with lamivudine, IFN-? and combination of LMV + IFN-? respectively), and 27 patients for CHC (3, 13 and 11 patients were treated with Ribavirin, IFN-? and combination therapy (RBV+ IFN-?) respectively].These patients were followed up for 6 months. By using ELISA technique, levels of IL-6, IL-10, IFN-? and TNF-? were measured in vivo and in vitro (supernatant of PBMCs stimulated with PHA) and compared with healthy control. The mean level of IL-6, IL-10 and TNF-? in CHB patients showed significant differences (P

In Vitro and In Vivo Renoprotective Effects of Telbivudine in Chronic Hepatitis B Patients Receiving Nucleotide Analogue

2019 ◽  
Vol 64 (12) ◽  
pp. 3630-3641
Author(s):  
Lung-Yi Mak ◽  
Sze-Hang Liu ◽  
Desmond Yat-Hin Yap ◽  
Wai-Kay Seto ◽  
Danny Ka-Ho Wong ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis B ◽  
Chronic Hepatitis B ◽  
Nucleotide Analogue
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