Cross talk between hepatitis B virus and innate immunity of hepatocytes

Abstract

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

Many Ways to Communicate—Crosstalk between the HBV-Infected Cell and Its Environment

“…In addition to efficient immune evasion, the virus seems to actively suppress different signalling pathways that are activated in response to innate sensing of a viral infection. Most of these effects are the result of direct interactions of the viral proteins, and of HBV-induced miRNAs [ 71 , 72 , 73 ]. For example, direct immunosuppression by HbsAg itself, which is the main component of HBV-SVPs, has been reported [ 74 , 75 ].…”

Binary split fluorescent biosensor based on lettuce DNA aptamer for label-free and enzyme-free analysis of hepatitis B viral DNA

“…4,5 Currently, although the existence of hepatitis B vaccines and mature vaccination regimes have been established to protect against HBV infection, HBV is still considered a type of stealth virus that deregulates the innate and adaptive antiviral immune response. [6][7][8][9] Thereby, it is difficult to nd a facile strategy to evaluate the gradient of HBV infection and for the early diagnosis of infected viral hosts. Notably, the viral life cycle during HBV infection is directly characterized by the persistent proliferation and delivery of the viral DNA genome.…”

Regulation of Pattern-Recognition Receptor Signaling by HBX During Hepatitis B Virus Infection

“…Generally, once sensitized by the virus, these PRRs can initiate the activation of multiple intracellular signaling pathways to produce interferons (IFNs), which further stimulate the sensitization of the Janus kinasesignal transducer and activator of transcription (JAK-STAT) signaling to participate in the inherent antiviral immune response. Additionally, these PRRs can stimulate the production of inflammatory cytokines induced by the nuclear factor kB (NF-kB) pathway to resist the virus (11,12). However, accumulating evidence suggests that to maintain persistent infection, the virus has evolved a variety of strategies to overcome the host antiviral responses mediated by PRR components, such as TLRs, cytosolic DNA sensors, RLRs, and NLRs, as well as their downstream pathways, including the JAK-STAT and NF-kB pathways, to facilitate viral replication and liver pathogenesis (13)(14)(15)(16).…”