Description and purpose
Chronic HDV infection causes the most severe form of viral hepatitis. The outcome of chronic HDV infection seems to be mainly dictated by the host immune system and its adaptive arm represents a key determinant of virus control or persistence. Based on these premises, the final objective of this proposal is to gain novel mechanistic information on T cell dysfunction in HDV/HBV coinfection and to define novel molecular targets for individualized therapies based on T cell functional reconstitution.
Purpose
- To unravel the virological determinants of HDV persistence, pathogenesis and treatment response
- Deciphering the genetic asset of HDV and its role in escaping viral surveillance by CD8 T cells
- To thoroughly characterize HDV- and HBV-specific T-cell responses in patients with chronic HBV-HDV co-infection and monitor their functional changes during Bulevirtide treatment
- To define the transcriptional and molecular signatures of CD8+ T-cell dysfunction in patients with chronic HBV/HDV co-infection.
Expected results
A better understanding of the immunological and virological mechanisms of HDV persistence and pathogenesis is therefore crucial to define the clinical outcome of HDV infection and to optimize therapeutic strategies.
This project will provide a unique and unprecedented opportunity to integrate clinical, immunological and virological parameters with the goal of identifying key factors underlying the clinical outcome of patients with chronic HDV infection and response to treatment with Bulevirtide.
Achieved results
Blood samples are currently being collected from patients with chronic HBV/HDV co-infection. Peripheral blood mononuclear cells were isolated and cryopreserved until the day of analysis. Experiments are ongoing to evaluate HDV- and HBV-specific T-cell responses by flow cytometry and FluoroSPOT analysis, using pools of short overlapping peptides covering the proteome of HBV and HDV in patients with chronic HBV-HDV co-infection and monitor their functional changes during Bulevirtide treatment.
