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.