Virus-specific T cell dysfunction is an important determinant of virus persistence in HBV infection and chronic exposure to high antigen loads is likely involved in altering the function of costimulatory pathways and regulatory T cell subsets/cytokines. We have performed the first transcriptome analysis of HBV-specific and total CD8 T cells from chronic HBV patients and identified specific dysregulated genes and cellular functions that represent potential targets for functional T cell restoration strategies. The main goals of this project are to functionally validate genes and pathways revealed by gene expression profiling and to extend this analysis to chronic patients under nucleos(t)ide analogues (NUC) therapy. This will allow to gain the information that is necessary to design novel combination therapies for naïve and NUC treated patients through the targeted manipulation of complementary regulatory pathways.
Fisicaro, Paola, Barili, Valeria, Montanini, Barbara, Acerbi, Greta, Ferracin, Manuela, Guerrieri, Francesca, Salerno, Debora, Boni, Carolina, Massari, Marco, Cavallo, M Cristina, Grossi, Glenda, Giuberti, Tiziana, Lampertico, Pietro, Missale, Gabriele, Levrero, Massimo, Ottonello, Simone, Ferrari, Carlo (2017)
Targeting mitochondrial dysfunction can restore antiviral activity of exhausted HBV-specific CD8 T cells in chronic hepatitis B.