Title:Assessment of new E2 protein domain interaction with PKR protein to control IFN signaling
VOLUME: 18
Author(s):Behzad Dehghani, Tayebeh Hashempour*, Zahra Mousavi, Zahra Hasanshahi, Javad Moayedi and Shahin Merat
Affiliation:Shiraz HIV/AIDS Research Center, Institute of Health, Shiraz University of Medical Sciences, Shiraz,, Shiraz HIV/AIDS Research Center, Institute of Health, Shiraz University of Medical Sciences, Shiraz,, Shiraz HIV/AIDS Research Center, Institute of Health, Shiraz University of Medical Sciences, Shiraz,, Shiraz HIV/AIDS Research Center, Institute of Health, Shiraz University of Medical Sciences, Shiraz,, Shiraz HIV/AIDS Research Center, Institute of Health, Shiraz University of Medical Sciences, Shiraz,, Liver and Pancreatobiliary Diseases Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran
Keywords:HCV, E2, PePHD, Drug resistance, Bioinformatics, IFNHCV, E2, PePHD, Drug resistance, Bioinformatics, IFN
Abstract:Introduction: Controversy exists regarding the impact of phosphorylation homology domain (PePHD) of Hepatitis
C virus (HCV) E2 protein on the interruption of antiviral signaling pathway. A mechanisms 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.
Methodology: 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 which is responsible for binding to PKR protein and is important to 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.
