Innate immunity and HBV persistence

Abstract

Hepatitis B virus (HBV) causes chronic infections that are associated with immune dysfunction. Though T cell impairment is perhaps the most prominent immune change contributing to viral persistence, HBV interaction with the innate immune system is also likely key, as the lack of effective innate immunity has functional consequences that promote chronic infection. In addition to an intrinsic ability to fight viral infections, the innate immune system also impacts T cell responses and other adaptive immune mechanisms critical for HBV control. Therefore, it is essential to understand the relationships between HBV and innate immunity, as these interactions may be useful immunotherapeutic targets to manage the infection.

Figure 1.. Therapeutic impacts of innate immune cells and cytokines on HBV replication.

Stimulating IFN-α/β or IFN-λ production by hepatocytes or DCs with RLR or TLR agonists, or activating IFN-γ production by T cells, NK cells, or MAIT cells may directly inhibit HBV replication in hepatocytes. In addition to activating innate antiviral mechanisms, IFN-α/β production may also stimulate virus-specific intrahepatic T cell responses. These T cell responses may be further enhanced by inhibiting the negative regulatory activities of MDSCs and NK cells or by altering macrophage function, which may also reduce immunopathology.