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Hepatitis E rORF2p stimulated and unstimulated peripheral expression profiling in patients with self-limiting
Sanjay B Rathod1, Anuradha S Tripathy1
1Hepatitis Group, National Institute of Virology, Pune, 130/1, Sus Road, Pashan, Pune, Maharashtra 411021, India.
Insights
Peripheral lymphocytes play a key role in hepatitis E virus (HEV) infection. This study found elevated immune markers on peripheral blood mononuclear cells (PBMCs) in acute HEV patients, suggesting their involvement in immune response regulation.
Area of Science:
- Immunology
- Virology
- Molecular Biology
Background:
- Hepatitis E virus (HEV) infection is a significant global health concern.
- The precise role of peripheral lymphocytes in HEV pathogenesis remains incompletely understood.
- Understanding immune cell dynamics is crucial for managing HEV infection.
Purpose of the Study:
- To investigate immunophenotypic and gene expression alterations in peripheral lymphocytes during acute and resolved HEV infection.
- To identify key immune markers involved in the pathogenesis and resolution of HEV.
- To elucidate the role of T regulatory cells (Treg) and associated cytokines in HEV infection.
Main Methods:
- Analysis of peripheral blood mononuclear cells (PBMCs) from 43 acute HEV patients, 30 recovered individuals, and 43 controls.
- Flow cytometry was used to assess immunophenotypic expressions of immune markers.
- TaqMan Low Density Array was employed for gene expression profiling of various immune-related genes.
- PBMCs were analyzed both unstimulated and stimulated with HEV recombinant open reading frame 2 protein (rORF2p).
Main Results:
- Significant elevations in CTLA-4, GITR, CD103, CD25, CD69, IL10, and TGF-β1 were observed on PBMCs of acute HEV patients.
- TGF-β1 was also elevated in recovered individuals.
- Gene expression analysis revealed upregulation of CD25, PD1, CD103, CCR4, IL10, and TGF-β1 in PBMCs of acute patients upon stimulation.
- These findings indicate increased expression of inhibitory, integrin, activatory, and Treg-associated cytokine genes.
Conclusions:
- Peripheral lymphocytes, particularly through upregulated inhibitory, integrin, activatory, and Treg-associated cytokine genes, are significantly involved in modulating the immune response during self-limiting hepatitis E.
- The identified immune markers provide insights into the fine-tuning of immune responses in HEV infection.
- This study enhances the understanding of lymphocyte involvement in HEV pathogenesis and resolution.
Abstract:
To improve the current knowledge on the involvement of peripheral lymphocytes in hepatitis E virus (HEV) associated pathogenesis, we analyzed alterations in (1) immunophenotypic expressions (by flow cytometry) and (2) gene expression patterns (by TaqMan Low Density Array) of activatory, inhibitory, integrin, homing, ectonucleotidase machinery, costimulatory, inflammatory markers, and T regulatory cells (Treg) associated cytokines on HEV rORF2p stimulated and unstimulated PBMCs of 43 acute HEV patients, 30 recovered individuals, and 43 controls. The phenotypic expressions of key molecules CTLA-4, GITR, CD103, CD25, CD69, IL10 and TGF- β 1 in the acute patients and TGF- β 1 in the recovered individuals were significantly elevated on both unstimulated and stimulated PBMCs. Gene expression array data revealed upregulations of CD25, PD1, CD103, CCR4, IL10, and TGF- β 1 on both unstimulated and HEV rORF2p stimulated PBMCs of acute patients. The observed upregulations of inhibitory, integrin, activatory, and Treg-associated cytokine genes on the PBMCs of acute HEV patients complemented by their frequency data suggest them as the major players in the fine-tuning of immune response in self-limiting hepatitis E infection.
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