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Structural Modification in Hepatitis C Virus Envelope Protein; Potential Viral Strategy Against Interferon Therapy

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Abstract

Interferons (IFNs) are the main part of the immune system as a defensive response to viral infection. The phosphorylation domain of Hepatitis C virus (HCV) E2 envelope glycoprotein is homologous to the host key enzymes in IFN-mediated response. So, if host kinases show no preference on E2 protein phosphorylation over IFN triggering factors, the IFN pathway would be competently inhibited. The aim of this study was to see if the resistance of HCV infected patients to IFN-therapy has something to do with HCV E2 envelope glycoprotein. For this purpose, the partially sequenced HCV E2 proteins obtained from 15 patients that were confirmed to be sustainable, semi-resistant (patients with relapsing infection) and resistant to IFN-therapy. The peptide sequences from 15 patients were analysed as a matter of homology, physicochemical properties and predicted structures using MEGA4 software, ProtParam, PSIPRED and I-TASSER tools, respectively. Then, certain point mutations introduced to sequences that acquired from patients resistant to IFN-therapy. Replacement of Asp 653 with Asn 653 in R1 at C-terminal of the E2 protein changes secondary and tertiary structures of downstream regions of E2 protein. Although the sequence of PKR-eIF2alpha phosphorylation homology domain in E2 protein remains intact during IFN therapy, its structure modifies in patients resistant to IFN-therapy, which then puts its phosphorylation potential in jeopardy. Therefore, structural modification in HCV E2 proteins, acquired form patients resistant to IFN-therapy, suggests a mechanism that shows how HCV gets resistant toward IFN-therapy.

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Authors and Affiliations

  1. Stem Cell Technology Research Center, Tehran, Iran

    Iman Rad

  2. Endocrine Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, No 10, Firoozeh St, Vali-asr Sq, Tehran, Iran

    Maryam Honardoost

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  1. Iman Rad
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  2. Maryam Honardoost
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Correspondence to Maryam Honardoost.

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Rad, I., Honardoost, M. Structural Modification in Hepatitis C Virus Envelope Protein; Potential Viral Strategy Against Interferon Therapy. Int J Pept Res Ther 26, 171–179 (2020). https://doi.org/10.1007/s10989-019-09826-2

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  • DOI: https://doi.org/10.1007/s10989-019-09826-2

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