Hepatocyte-intrinsic innate immunity in hepatitis B virus infection: A focused review

Chronic hepatitis B virus (HBV) infection remains a major health burden worldwide. To establish a persistence infection, HBV needs to evade both adaptive and innate immune surveillance. Multiple mechanisms for adaptive immunity evasion have been established, but how HBV evades the innate surveillance is less clear. There are three types of host cells involving in the innate immune responses against HBV infection: Hepatocytes, hepatic nonparenchymal cells and conventional innate immune cells. Among these, hepatocytes are the only target cells that are susceptible to HBV infection and the only confirmed site where HBV replication takes place. This review focuses on the hepatocyte-intrinsic innate immunity; one of the earliest host defense responses. After entering hepatocytes, the viral components can be sensed by the cellular pattern recognition receptors. This triggers downstream antiviral responses capable of inhibiting viral replication and even degrading the viral DNA genome directly or indirectly. However, HBV has evolved a variety of sophisticated strategies to evade intracellular immune defense, resulting in the establishment of infection. Here, we provide insights into the mechanisms of the intrinsic innate immune response of hepatocytes and how HBV escapes these defense mechanisms. Hopefully, this will lay the foundation for the development of novel anti-HBV therapies.