Innate immune targets of hepatitis B virus infection

Abstract

Approximately 400 million people are chronically infected with hepatitis B virus (HBV) globally despite the widespread immunization of HBV vaccine and the development of antiviral therapies. The immunopathogenesis of HBV infection is initiated and driven by complexed interactions between the host immune system and the virus. Host immune responses to viral particles and proteins are regarded as the main determinants of viral clearance or persistent infection and hepatocyte injury. Innate immune system is the first defending line of host preventing from virus invasion. It is acknowledged that HBV has developed active tactics to escape innate immune recognition or actively interfere with innate immune signaling pathways and induce immunosuppression, which favor their replication. HBV reduces the expression of pattern-recognition receptors in the innate immune cells in humans. Also, HBV may interrupt different parts of antiviral signaling pathways, leading to the reduced production of antiviral cytokines such as interferons that contribute to HBV immunopathogenesis. A full comprehension of the mechanisms as to how HBV inactivates various elements of the innate immune response to initiate and maintain a persistent infection can be helpful in designing new immunotherapeutic methods for preventing and eradicating the virus. In this review, we aimed to summarize different branches the innate immune targeted by HBV infection. The review paper provides evidence that multiple components of immune responses should be activated in combination with antiviral therapy to disrupt the tolerance to HBV for eliminating HBV infection.

Keywords: Hepatitis B virus; Infection; Targets; Innate immune response; Signaling pathway

Core tip: The pathogenesis of hepatitis B virus (HBV) infection is initiated and driven by complicated interplays between the virus and the host immune system. HBV DNA and different HBV proteins have various effects on different arms of innate immune system. The extent of HBV replication as well as the amounts of circulating HBV antigens and different source of HBV proteins have heterogenous effects on innate immune responses and antiviral signaling pathways. Other factors, such as liver inflammation may also have impact on innate immune response. Multiple components of immune responses should be activated in combination with antiviral therapy to disrupt the tolerance to HBV for eliminating HBV infection.