Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5910665 | Infection, Genetics and Evolution | 2013 | 7 Pages |
Abstract
Hepatitis C virus (HCV) is one of the foremost causes of chronic liver disease affecting over 300Â million globally. HCV contains a positive-stranded RNA of â¼9600Â nt and is surrounded by the 5â² and 3â²untranslated 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.
Keywords
TelaprevireIF2αSOCST-helperTLR3dsRNAIRESIRF3ISGPKRISREISDRIRRDRBOCIFN-α receptorToll like receptor 3repressor element-1 silencing transcription factorSVRUPRNF-κBIFNARSTATinterferonInterferon (IFN)IFNinterleukinReSTBoceprevircluster of differentiationinternal ribosome entry sitesuppressor of cytokine signalingendoplasmic reticulumeukaryotic initiation factor 2αInterferon regulatory factor 3nuclear factor kappa-light-chain-enhancer of activated B cellsSignal transducer and activator of transcriptionInsulin resistanceUntranslated regionsUTR یا untranslated regions interferon sensitivity determining regionProtease inhibitorTVRHCVHepatitis C virusHepatitis C virus (HCV)sustained virological responseUnfolded protein responseprotein kinase RSingle nucleotide polymorphism (SNP)Single nucleotide polymorphismsSNPGenotypeGas
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Authors
Hanadi Qashqari, Amany Al-Mars, Adeel Chaudhary, Adel Abuzenadah, Ghazi Damanhouri, Mohammed Alqahtani, Maged Mahmoud, Maysaa El Sayed Zaki, Kaneez Fatima, Ishtiaq Qadri,