Innate immune responses in hepatitis B virus (HBV) infection

Abstract

Hepatitis B virus (HBV) infection has a low rate of chronicity compared to HCV infection, but chronic liver inflammation can evolve to life threatening complications. Experimental data from HBV infected chimpanzees and HBV transgenic mice have indicated that cytotoxic T cells are the main cell type responsible for inhibition of viral replication, but also for hepatocyte lysis during chronic HBV infection. Their lower activation and impaired function in later stages of infection was suggested as a possible mechanism that allowed for low levels of viral replication. The lack of an interferon response in these models also indicated the importance of adaptive immunity in clearing the infection. Increased knowledge of the signalling pathways and pathogen associated molecular patterns that govern activation of innate immunity in the early stages of viral infections in general has led to a re-evaluation of the innate immune system in HBV infection. Numerous studies have shown that HBV employs active strategies to evade innate immune responses and induce immunosuppression. Some of the immune components targeted by HBV include dendritic cells, natural killer cells, T regulatory cells and signalling pathways of the interferon response. This review will present the current understanding of innate immunity in HBV infection and of the challenges associated with clearing of the HBV infection.

Serological and molecular epidemiological outcomes after two decades of universal infant hepatitis B virus (HBV) vaccination in Nunavut, Canada

“…Initial HBV infection does not always prompt the host innate immune response, allowing HBV to infect host hepatocytes and incubate, which lasts weeks or sometimes months, leading to high viremia [12]. This may explain the high rate of chronicity in infants with immature immune systems, as infected adults can achieve viral clearance by mounting rapid humoral and cellular immune responses, and have a much lower risk of chronicity [13]. As viremia increases during the incubation phase, effector molecules and cells of the adaptive immune response eventually become activated.…”

Role of Tim-3 in hepatitis B virus infection: An overview

“…However, impairments in the adaptive immune response cannot explain all events that occur during HBV infection, because various components of the innate immune system also participate in disease progression. Indeed, the activation of dendritic cells (DCs), natural killer cells (NKs) and macrophages during acute infection leads to a bona fide clinical outcome, whereas persistent HBV infection at least partly results from dysregulation of the innate immune response at early stages of infection [7] . Therefore, studying the interaction between HBV and host immunity and uncovering the reason why the immune response is dysregulated in HBV infection are critical.…”

New horizon for radical cure of chronic hepatitis B virus infection

“…Innate immune system such as pattern recognition rece ptors, macrophages, DCs, natural killer cells or natural killer T cells are involved in the pathogenesis of HBV infection especially at an early stage of infection [61,62] . HBV has been shown to alter the function of macrophages by modulating the secretion of cytokines [63,64] or type1 IFN gene expression [64] .…”