title: GB Virus C/Hepatitis G Virus Envelope Glycoprotein E2: Computational Molecular Features and Immunoinformatics Study.
abstract: BACKGROUND
  GB virus C (GBV-C) or hepatitis G virus (HGV) is an enveloped, RNA positive-stranded flavivirus-like particle. E2 envelope protein of GBV-C plays an important role in virus entry into the cytosol, genotyping and as a marker for diagnosing GBV-C infections. Also, there is discussion on relations between E2 protein and gp41 protein of HIV. The purposes of our study are to multi aspect molecular evaluation of GB virus C E2 protein from its characteristics, mutations, structures and antigenicity which would help to new directions for future researches.
  
  
  METHODS
  Briefly, steps followed here were; retrieving reference sequences of E2 protein, entropy plot evaluation for finding the mutational /conservative regions, analyzing potential Glycosylation, Phosphorylation and Palmitoylation sites, prediction of primary, secondary and tertiary structures, then amino acid distributions and transmembrane topology, prediction of T and B cell epitopes, and finally visualization of epitopes and variations regions in 3D structure.
  
  
  RESULTS
  Based on the entropy plot, 3 hypervariable regions (HVR) observed along E2 protein located in residues 133-135, 256-260 and 279-281. Analyzing primary structure of protein sequence revealed basic nature, instability, and low hydrophilicity of this protein. Transmembrane topology prediction showed that residues 257-270 presented outside, while residues 234- 256 and 271-293 were transmembrane regions. Just one N-glycosylation site, 5 potential phosphorylated peptides and two palmitoylation were found. Secondary structure revealed that this protein has 6 α-helix, 12 β-strand 17 Coil structures. Prediction of T-cell epitopes based on HLA-A*02:01 showed that epitope NH3-LLLDFVFVL-COOH is the best antigen icepitope. Comparative analysis for consensus B-cell epitopes regarding transmembrane topology, based on physico-chemical and machine learning approaches revealed that residue 231- 296 (NH2- EARLVPLILLLLWWWVNQLAVLGLPAVEAAVAGEVFAGPALSWCLGLPVVSMILGLANLVLYFRWL-COOH) is most effective and probable B cell epitope for E2 protein.
  
  
  CONCLUSIONS
  The comprehensive analysis of a protein with important roles has never been easy, and in case of E2 envelope glycoprotein of HGV, there is no much data on its molecular and immunological features, clinical significance and its pathogenic potential in hepatitis or any other GBV-C related diseases. So, results of the present study may explain some structural, physiological and immunological functions of this protein in GBV-C, as well as designing new diagnostic kits and besides, help to better understandingE2 protein characteristic and other members of Flavivirus family, especially HCV.
authors.affiliation: Department of Immunology, University of Tehran, Tehran, IR Iran.
authors.forename: Mohammad Mahdi
authors.initials: MM
authors.lastname: Ranjbar
authors.affiliation: Department of Immunology, School of Medicine, AJA University of Medical Sciences, Tehran, IR Iran.
authors.forename: Khodayar
authors.initials: K
authors.lastname: Ghorban
authors.affiliation: Middle East Liver Diseases Center (MELD), Tehran, IR Iran ; Baqiyatallah Research Center for Gastroenterology and Liver Diseases, Baqiyatallh University of Medical Sciences, Tehran, IR Iran.
authors.forename: Seyed Moayed
authors.initials: SM
authors.lastname: Alavian
authors.affiliation: Department of Virology, Tehran University of Medical Sciences, Tehran, IR Iran.
authors.forename: Hossein
authors.initials: H
authors.lastname: Keyvani
authors.affiliation: Department of Infectious Diseases, School of Medicine, AJA University of Medical Sciences, Tehran, IR Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Dadmanesh
authors.affiliation: Department of Computer Sciences, University of Nevada, Reno, USA.
authors.forename: Abbas
authors.initials: A
authors.lastname: Roayaei Ardakany
authors.affiliation: Razi Vaccine and Serum Research Institute, Karaj Branch, Karaj, IR Iran.
authors.forename: Mohammad Hassan
authors.initials: MH
authors.lastname: Motedayen
authors.affiliation: Department of Agriculture, Payame Noor University, Yazd, IR Iran.
authors.forename: Alireza
authors.initials: A
authors.lastname: Sazmand
keywords: GB virus C; Immunoinformatics; glycoprotein E2, GB virus C