Figure 2.

Interferon-α (IFN-α) has been shown to target different steps of HBV cycle either by generic antiviral mechanisms (1), via activation of the IFN Sensitive Genes (ISGs), or by specific blocking (2) and degrading (3) replication competent core particles, as well as pre-genomic-RNA (4) and nuclear covalently closed circular DNA (cccDNA), or by inhibition of cccDNA transcription (5). The main immune-modulatory activity of IFN-α consists in boosting the innate immune response (6) by stimulating Natural Killer (NK) cells, whereas IFN-α appears unable to restore the effector function of the HBV specific cytotoxic T cells (CTLs). Nevertheless, a late improvement of the adaptive immune responses (7), involving the functions of Kupfer Cells (KC), T Helper lymphocytes and Plasmacytoid Dendritic Cells (PDC), is observed in responder patients.