Abstract
For many years, the standard of treatment for hepatitis C virus (HCV) infection was a combination of pegylated interferon alpha (Peg-IFN-α) and ribavirin for 24–48 weeks. This treatment regimen results in a sustained virologic response (SVR) rate in about 50 % of cases. The failure of IFN-α-based therapy to eliminate HCV is a result of multiple factors including a suboptimal treatment regimen, severity of HCV-related diseases, host factors and viral factors. In recent years, advances in HCV cell culture have contributed to a better understanding of the viral life cycle, which has led to the development of a number of direct-acting antiviral agents (DAAs) that target specific key components of viral replication, such as HCV NS3/4A, HCV NS5A, and HCV NS5B proteins. To date, several new drugs have been approved for the treatment of HCV infection. Application of DAAs with IFN-based or IFN-free regimens has increased the SVR rate up to >90 % and has allowed treatment duration to be shortened to 12–24 weeks. The impact of HCV proteins in response to IFN-based and IFN-free therapies has been described in many reports. This review summarizes and updates knowledge on molecular mechanisms of HCV proteins involved in anti-IFN activity as well as examining amino acid variations and mutations in several regions of HCV proteins associated with the response to IFN-based therapy and pattern of resistance associated amino acid variants (RAV) to antiviral agents.
Highlights
Hepatitis C virus (HCV) belongs to the Hepacivirus genus which is part of the Flaviviridae family
Previous studies have demonstrated that substitutions of amino acid residues 70 (R70Q) and/or 91 (L91M) in the core region were significant factors independently associated with a non-virological response (NVR) to IFN and ribavirin combination therapy [104, 105]
A correlation of a high number of mutations in a IFN-α sensitivity determining region (ISDR; codons 2209–2248) (Fig. 3) comprising 40 amino acids within the C-terminal part of the NS5A protein and sustained virologic response (SVR) to IFN-α monotherapy in HCV genotype 1b infected patients was described in Japan [124]
Summary
Hepatitis C virus (HCV) belongs to the Hepacivirus genus which is part of the Flaviviridae family. Since 2011, a number of direct acting antiviral agents (DAAs), which target hepatitis C viral proteins including NS3/4A, NS5A and NS5B, have been used to improve the treatment of HCV infection.
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