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Introduction
An efficient control of virus infections requires the coordinate action of both innate and adaptive immune responses. Innate immunity has evolved to rapidly recognise viral nucleic acids, viral proteins and tissue damage. It induces an antiviral state on infected cells by producing type I interferons (IFN), decreases the pool of infected cells by directing natural killer (NK) cell-mediated killing of viral infected cells, and supports the efficient maturation and site recruitment of adaptive immunity through production of pro-inflammatory cytokines and chemokines. 1 These mechanisms reduce virus spread until the adaptive branch of immunity takes the stage. Adaptive immunity acts through functional maturation and expansion of distinct B and T cell clones able to specifically recognise the infectious agents, a process that necessitates time. This process leads to the control of infection and generates a memory response which increases the host ability to block subsequent infections with the same pathogens.
The different pathogens cause an assortment of clinical conditions, and they have evolved different strategies to escape host immunity; hepatitis B virus (HBV) has undoubtedly developed its own peculiar tactics. 2
While most viruses enter a logarithmic phase of propagation immediately after infection (eg, hepatitis C virus (HCV), HIV, human cytomegalovirus (HCMV), influenza virus, dengue virus), HBV infection is characterised by a delayed amplification of HBV replication and spread. Febrile symptoms occur immediately in many acute viral infections, while acute HBV infection is mainly asymptomatic. Finally, while viral persistence is frequently associated with low viral load and protein expression (eg, HCV, HCMV, Epstein-Barr virus), chronic HBV infection is typically characterised by the production of extremely high quantities of viral proteins (HBsAg, HBeAg). 3 4 We will summarise how HBV deals with host immunity and we will discuss how we can harness the immune response to potentially achieve infection control.
Innate immunity against HBV: lack of recognition or active inhibition?
Our knowledge of anti-HBV innate immune responses is still hampered by technical limitations. Data obtained during natural infection in patients are limited by the difficulty in recruiting patients at the earliest presymptomatic stages of acute HBV infection (reviewed in Bertoletti et al 2 ). In addition, an in vitro infection system for HBV in non-transformed hepatocytes is not widely available, its infection efficiency is poor...