Current progress in host innate and adaptive immunity against hepatitis C virus infection

Abstract

Hepatitis C virus (HCV) infects more than 170 million people worldwide and is the main cause of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. Although the newly developed direct-acting antivirals (DAAs) have transformed the treatment of HCV infection, controlling HCV infection on a global scale remains a challenge because of the high cost, low resistance barrier of DAAs and lack of HCV vaccine. The host immune responses associated with HCV infection, especially HCV-specific T cellular immunity, determine the outcome of HCV infection: either acute or chronic infection. It is important to fully interpret the immunopathogenesis of HCV infection and consequently to exploit effective strategies to eliminate HCV. Here, we review the current progress in HCV immunology, which will deepen our understanding of the spectrum of HCV infection and immunity in humans.

Risk of Hepatocellular Carcinoma after HCV Clearance by Direct-Acting Antivirals Treatment Predictive Factors and Role of Epigenetics

“…In fact, while the previous therapeutic regimens based on the use of Interferon (IFN) were characterized by a sustained virological response (SVR) of 40–50%, DAAs allow an SVR almost in 100% of patients [ 2 , 3 , 4 ]. The result is of utmost clinical importance as HCV clearance is expected to prevent most of the serious complications due to progression of chronic hepatic C, as well as to the associated immune system dysregulation and chronic systemic inflammatory response [ 5 , 6 , 7 , 8 , 9 , 10 , 11 ]. However, DAAs are likely to affect the immune response, but the underlying biological mechanisms remain largely unexplored [ 12 , 13 ].…”

Proprotein convertase subtilisin/kexin type 9 inhibits interferon β expression through interacting with ATF‐2

“…Host innate immune system acts as the first line to fight against viral infections, such as hepatitis C virus (HCV) infection. Invading HCV RNA can be sensed by pathogen recognition receptors (PRRs), including toll‐like receptors and retinoic acid‐inducible gene I‐like receptors, which sequentially activate downstream interferon (IFN) regulatory factor‐3 (IRF‐3) to induce type I, type III IFN, and IFN‐stimulated genes (ISGs) production . Secreted IFNs can act on neighboring cells to activate Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway to induce transcription of numerous ISGs, resulting in HCV replication inhibition .…”

Hepatitis C Vaccine Development in the Era of Direct‐Acting Antivirals

“…CD8 + T cells specific to HCV can clear the virus through the cytolytic mechanism (causing apoptosis of infected hepatocytes) or the noncytolytic mechanism (suppressing HCV replication through secreted cytokines). However, CD8 + T cell exhaustion occurs in HCV infection because of upregulation of T cell–inhibitory receptors . The majority of currently registered clinical trials with a known status are of vaccines using T cell–mediated immunity (Table ) with some encouraging results from phase 2 studies .…”