Affiliation:
1. Shiraz HIV/AIDS Research Center, Institute of Health, Shiraz University of Medical Sciences, Shiraz, Iran
2. Liver and Pancreatobiliary Diseases Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
Abstract
Introduction:
Controversy exists regarding the impact of Phosphorylation Homology
Domain (PePHD) of Hepatitis C Virus (HCV) E2 protein on the interruption of the antiviral signaling
pathway. A mechanism by which the virus evades the antiviral effect of interferon (IFN) alpha
involves protein kinase (PKR) eukaryotic Initiation Factor 2 alpha (eIF2a) PePHD. By binding to
PKR, PePHD inhibits its activity and, therefore, causes the virus to evade the antiviral activity of
IFN. This study aimed to clarify the inconsistency of different conclusions reached in previous
studies using reliable bioinformatics tools.
Methods:
Fifty-eight Iranian patients infected with HCV genotypes 1a and 3a and 58 healthy control
individuals were examined. Plasma viral RNA was used to amplify and sequence the HCV E2
gene; also, HCV viral load, genotyping, IL-28B genotyping, alanine Aminotransferase (ALT), and
aspartate aminotransferase (AST) test were determined. Bioinformatics tools determined the physicochemical
properties, B-cell epitopes, post-modification changes, and secondary/tertiary structures,
and also evaluated the interactions between E2 and PePHD regions.
Results:
The results showed a new domain that is responsible for binding to PKR protein and is important
to the intrigued antiviral response. Physicochemical features and post-modifications were
defined, showing that E2 is highly phosphorylated and there were numerous possible disulfide
bonds. Secondary and tertiary structures for E2 protein were constructed. No significant relationship
between ALT and AST and treatment failure was detected.
Conclusions:
Docking analysis showed a new domain in E2 protein that can be involved in the interaction
between PKR and E2 protein. This finding may justify our results revealing the non-significant
relationship between mutations in PePHD and treatment failure.
Funder
Shiraz University of Medical Sciences
Publisher
Bentham Science Publishers Ltd.
Subject
Molecular Biology,Biochemistry
Cited by
1 articles.
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