Innate immunity plays a major role in controlling viral infections. Recent exploration of sodium taurocholate co-transporting polypeptide receptor as specific hepatitis B virus (HBV) receptor in human hepatocytes has provided appropriate cell culture tools to study the innate immunity of hepatocytes and its cross talk with HBV. In this review, we give a brief update on interaction between HBV and innate immunity using the currently available in vitro cellular models that support the complete life cycle of HBV. We will discuss how HBV can act as a 'stealth' virus to counteract the innate immune responses mediated by the pathogen recognition receptors of hepatocytes and escape the first line of surveillance of the host immune system. We give an overview of the cellular components of innate immunity that present in these in vitro models and discuss how activating these innate immunity components may contribute to the eradication of HBV infection.
K E Y W O R D Scell culture models, hepatitis B virus (HBV), innate immunity, pattern recognition receptors, toll-like receptors
| INTRODUCTIONHepatitis B virus (HBV) selectively infects hepatocytes of human liver. 1,2 Despite the effectiveness of hepatitis B vaccination, HBV is still a major public health problem with more than 240 million chronic carriers worldwide of whom almost a third are at high risk of developing serious HBV-related complications, such as liver cirrhosis and hepatocellular carcinoma (HCC). 3,4 The first line of defence against viruses is innate immunity. Most viruses are sensed and detected by innate immunity at early stages of infection, leading to initiation of anti-viral responses such as production of interferons (IFNs) and other pro-inflammatory cytokines. [5][6][7] Induction of these cytokines during viral infection occurs through two distinct signalling pathways: subfamilies of toll-like receptors (TLRs) as well as other innate immunity signalling pathways that sense RNA or DNA of viruses, such as retinoic acid inducible gene I (RIG-I)/melanoma differentiation-associated protein 5 (MDA5) and cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)/STING. 6,8 However, HBV has been considered a 'stealth' virus and before hepatocytes can sense and respond to the