Host–virus interactions in hepatitis B and hepatitis C infection

Abstract

Hepatitis B virus (HBV) and hepatitis C virus (HCV) are among the most endemic pathogens worldwide, with more than 500 million people globally currently infected with these viruses. These pathogens can cause acute and chronic hepatitis that progress to liver cirrhosis or hepatocellular carcinoma. Both viruses utilize multifaceted strategies to evade the host surveillance system and fall below the immunological radar. HBV has developed specific strategies to evade recognition by the innate immune system and is acknowledged to be a stealth virus. However, extensive research has revealed that HBV is recognized by dendritic cells (DCs) and natural killer (NK) cells. Indoleamine-2, 3-dioxygenase is an enforcer of sequential immune reactions in acute hepatitis B, and this molecule has been shown to be induced by the interaction of HBV-infected hepatocytes, DCs, and NK cells. The interleukin-28B genotype has been reported to influence HCV eradication either therapeutically or spontaneously, but the biological function of its gene product, a type-III interferon (IFN-k3), remains to be elucidated. Human BDCA3 ? DCs have also been shown to be a potent producer of IFN-k3 in HCV infection, suggesting the possibility that BDCA3 ? DCs could play a key role in developing therapeutic HCV vaccine. Here we review the current state of research on immune responses against HBV and HCV infection, with a specific focus on innate immunity. A comprehensive study based on clinical samples is urgently needed to improve our understanding of the immune mechanisms associated with viral control and thus to develop novel immune modulatory therapies to cure chronic HBV and HCV infection.

Interferon Lambda: Modulating Immunity in Infectious Diseases

“…Studies on the impact of IFN-λs in clinical scenarios have been dominated by the strong association of IFNL3/L4 SNPs with spontaneous clearance of HCV and IFN-α treatment response (79,80,87,90,103,111). Details on this important association have been reviewed in detail elsewhere (165)(166)(167). The association between IFN-λ SNPs and other infectious diseases is far less well explored.…”

Hepatic IFNL4 expression is associated with non‐response to interferon‐based therapy through the regulation of basal interferon‐stimulated gene expression in chronic hepatitis C patients

“…The innate immune system has essential roles in host antiviral defense against viral infection such as the hepatitis B (HBV) and hepatitis C (HCV) viruses . Viral infection induces the expression of intrinsic interferons (IFNs); thus, pegylated‐IFNα (PEG‐IFNα) has been used for the treatment of chronic hepatitis C (CHC) and hepatitis B (CHB) infections over the last two decades due to its potent antiviral effects via the regulation of IFN‐stimulated genes (ISGs), including antiviral, and immunoregulatory genes …”

Serum IFN-λ3 Levels Correlate with Serum Hepatitis C Virus RNA Levels in Symptomatic Patients with Acute Hepatitis C

“…Therefore, it may be that not only the existence or initiation of another innate immune system in addition to the rs8099917 favorable genotype, but also the activation of the adaptive immune system, is indispensable for successful HCV clearance. The roles of dendritic cells that harmonize the innate and adaptive immune system by stimulating natural killer cells and activating CD4 + and CD8 + T cells are also important, although further studies are required to evaluate the functions of dendritic cells in acute HCV infection [47] .…”