Understanding the molecular mechanism(s) of hepatitis C virus (HCV) induced interferon resistance.
Hepatitis C virus (HCV) is one of the foremost causes of chronic liver disease affecting over 300 million globally. HCV contains a positive-stranded RNA of ~9600 nt and is surrounded by the 5' and 3'untranslated regions (UTR). The only successful treatment regimen includes interferon (IFN) and ribavirin. Like many other viruses, HCV has also evolved various mechanisms to circumvent the IFN response by blocking (1) downstream signaling actions via STAT1, STAT2, IRF9 and JAK-STAT pathways and (2) repertoire of IFN Stimulatory Genes (ISGs). Several studies have identified complex host demographic and genetic factors as well as viral genetic heterogeneity associated with outcomes of IFN therapy. The genetic predispositions of over 2000 ISGS may render the patients to become resistant, thus identification of such parameters within a subset of population are necessary for management corollary. The ability of various HCV genotypes to diminish IFN antiviral responses plays critical role in the establishment of chronic infection at the acute stage of infection, thus highlighting importance of the resistance in HCV treated groups. The recently defined role of viral protein such as C, E2, NS3/NS4 and NS5A proteins in inducing the IFN resistance are discussed in this article. How the viral and host genetic composition and epistatic connectivity among polymorphic genomic sites synchronizes the evolutionary IFN resistance trend remains under investigation. However, these signals may have the potential to be employed for accurate prediction of therapeutic outcomes. In this review article, we accentuate the significance of host and viral components in IFN resistance with the aim to determine the successful outcome in patients.
['Qashqari|Hanadi|H|', 'Al-Mars|Amany|A|', 'Chaudhary|Adeel|A|', 'Abuzenadah|Adel|A|', 'Damanhouri|Ghazi|G|', 'Alqahtani|Mohammed|M|', 'Mahmoud|Maged|M|', 'El Sayed Zaki|Maysaa|M|', 'Fatima|Kaneez|K|', 'Qadri|Ishtiaq|I|']
D000998:Antiviral Agents D024882:Drug Resistance, Viral D005838:Genotype D016174:Hepacivirus D006526:Hepatitis C D054884:Host-Pathogen Interactions D006801:Humans D007372:Interferons D014764:Viral Proteins
Hepatitis C virus (HCV) hepatitis C virus HCV interferon UTR Interferon (IFN) IFN ISG genotype BOC CD DsRNA ER GAS GT IFN-stimulated response elements IFN-α receptor IFNAR IL IR IRES IRF3 IRRDR ISDR ISRE Interferon stimulatory genes (ISGs) NF-κb PI PKR PePHD Protein kinase R (PKR) RE-1 REST SNP SOCS STAT SVR Single nucleotide polymorphism (SNP) Suppressor of cell signaling (SOCS) T-helper TLR3 TVR Th UPR boceprevir cluster of differentiation double stranded RNA viruses eIF2α endoplasmic reticulum eukaryotic initiation factor 2α gamma interferon activation site insulin resistance interferon and ribavirin resistance determining region interferon regulatory factor 3 interferon sensitivity determining region interferon stimulatory genes interleukin internal ribosome entry site nuclear factor kappa-light-chain-enhancer of activated B cells phosphorylation homology domain protease inhibitor protein kinase R repressor element-1 repressor element-1 silencing transcription factor signal transducer and activator of transcription single nucleotide polymorphisms suppressor of cytokine signaling sustained virological response telaprevir toll like receptor 3 unfolded protein response untranslated regions