Understanding the molecular mechanism(s) of hepatitis C virus (HCV) induced interferon resistance |
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| Affiliation: | 1. King Fahd Medical Research Center, King Abdulaziz University, P.O. Box 80216, Jeddah 21589, Saudi Arabia;2. Center of Excellence in Genomic Medicine, King Abdulaziz University, P.O. Box 80216, Jeddah 21589, Saudi Arabia;3. Faculty of Applied Medical Sciences, King Abdulaziz University, P.O. Box 80216, Jeddah 21589, Saudi Arabia;4. Faculty of Medicine, Mansoura University, Egypt;5. IQ Institute of Infection and Immunity, Lahore, Pakistan;1. Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chia-Yi, Taiwan;2. School of Medicine, Tzuchi University, Hualien, Taiwan;3. Department of Life Science and Institute of Molecular Biology, National Chung Cheng University, No. 168, University Rd, Min-Hsiung, Chia-Yi, 62102, Taiwan;4. Department of Internal Medicine, National Cheng Kung University Medical College and Hospital, Tainan, Taiwan;5. Infectious Disease and Signaling Research Center, National Cheng Kung University, Tainan, Taiwan;1. Department of Epidemiology, Pre-clinical Research and Advanced Diagnostic, National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS, Rome, Italy;2. Clinical Department, National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS, Rome, Italy;1. Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases and Clinical Research Centre, Hvidovre Hospital and Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark |
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| Abstract: | ![]()
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. |
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| Keywords: | Hepatitis C virus (HCV) Interferon (IFN) Protein kinase R (PKR) Interferon stimulatory genes (ISGs) Suppressor of cell signaling (SOCS) Single nucleotide polymorphism (SNP) |
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