Mathematical model of antiviral immune response. I. Data analysis, generalized picture construction and parameters evaluation for hepatitis B

1991 ◽  
Vol 151 (1) ◽  
pp. 1-40 ◽  
Author(s):  
G.I. Marchuk ◽  
R.V. Petrov ◽  
A.A. Romanyukha ◽  
G.A. Bocharov
2019 ◽  
Vol 11 (2) ◽  
pp. 14-19 ◽  
Author(s):  
R. R. Khodzhibekov ◽  
O. N. Khokhlova ◽  
A. R. Reizis ◽  
G. M. Kozhevnikova

A new approach in understanding the mechanisms of immune response in viral hepatitis is the discovery of a unique type of immune cells – plasmocytoid dendritic cells (pDCs). Plasmocytoid dendritic cells (pDCs) are cells of lymphoid origin and morphologically resemble plasma cells. Functionally, they are professional IFN-a-producing cells that play an important role in antiviral immune response. Data on the mechanisms of PDCs participation in hepatitis B virus infection are few and contradictory. In chronic HBV infection, the role of pDCs remains mysterious and poorly understood with conflicting circulating blood pDCs results that show differently that they are not affected or reduced. However, functional disorders of pDCs were observed in patients with chronic HBV infection. The establishment of these mechanisms, as well as the search for the cause of hepatitis B virus latency and the formation of chronic infection remains one of the important and promising areas of scientific activities today.


Virology ◽  
2007 ◽  
Vol 361 (1) ◽  
pp. 141-148 ◽  
Author(s):  
Jeroen N. Stoop ◽  
Renate G. van der Molen ◽  
Ernst J. Kuipers ◽  
Johannes G. Kusters ◽  
Harry L.A. Janssen

2014 ◽  
Vol 59 (2) ◽  
pp. 1273-1281 ◽  
Author(s):  
Fang Guo ◽  
Yanxing Han ◽  
Xuesen Zhao ◽  
Jianghua Wang ◽  
Fei Liu ◽  
...  

ABSTRACTChronicity of hepatitis B virus (HBV) infection is due to the failure of a host to mount a sufficient immune response to clear the virus. The aim of this study was to identify small-molecular agonists of the pattern recognition receptor (PRR)-mediated innate immune response to control HBV infection. To achieve this goal, a coupled mouse macrophage and hepatocyte culture system mimicking the intrahepatic environment was established and used to screen small-molecular compounds that activate macrophages to produce cytokines, which in turn suppress HBV replication in a hepatocyte-derived stable cell line supporting HBV replication in a tetracycline-inducible manner. An agonist of the mouse stimulator of interferon (IFN) genes (STING), 5,6-dimethylxanthenone-4-acetic acid (DMXAA), was found to induce a robust cytokine response in macrophages that efficiently suppressed HBV replication in mouse hepatocytes by reducing the amount of cytoplasmic viral nucleocapsids. Profiling of cytokines induced by DMXAA and agonists of representative Toll-like receptors (TLRs) in mouse macrophages revealed that, unlike TLR agonists that induced a predominant inflammatory cytokine/chemokine response, the STING agonist induced a cytokine response dominated by type I IFNs. Moreover, as demonstrated in an HBV hydrodynamic mouse model, intraperitoneal administration of DMXAA significantly induced the expression of IFN-stimulated genes and reduced HBV DNA replication intermediates in the livers of mice. This study thus proves the concept that activation of the STING pathway induces an antiviral cytokine response against HBV and that the development of small-molecular human STING agonists as immunotherapeutic agents for treatment of chronic hepatitis B is warranted.


2018 ◽  
Vol 447 ◽  
pp. 98-110 ◽  
Author(s):  
F. Fatehi Chenar ◽  
Y.N. Kyrychko ◽  
K.B. Blyuss

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