Skip to main content

Advertisement

SpringerLink
Log in

Expression, immunogenicity and diagnostic value of envelope proteins from an Egyptian hepatitis C virus isolate

  • Original Article
  • Published:
Archives of Virology Aims and scope Submit manuscript

Abstract

The present work aimed at 1) characterization of the E1 and E2 proteins (HCV-E) from an Egyptian hepatitis C virus genotype 4a (HCV-4a) isolate at the molecular and immunological level, 2) in silico identification of the B- and T-cell epitopes responsible for the immunogenicity of HCV-E, and 3) evaluation of the diagnostic potential of both the recombinant HCV-E and antibodies raised using mammalian expression constructs encoding the protein. The region encoding the E1 and E2 proteins was amplified by RT-PCR from RNA isolated from blood of a human infected with HCV-4 and cloned into the pSC-TA plasmid, and the sequence was verified and used to construct a neighbor-joining phylogenetic tree. The translated nucleotide sequence was used to predict the HCV-E secondary structure using the PREDICT-PROTEIN server and PSI-PRED. A 3D model of HCV-E was generated using the online tool 3Dpro. B- and T-cell epitopes were predicted using the online tools BCPred and Epijen v1.0, respectively. The HCV-E-encoding sequence was later subcloned into the mammalian expression plasmid pQE, and the constructs that were generated were used to immunize mice in the absence and presence of adjuvants of plant origin. The maximum sequence identity obtained by nucleotide and protein BLAST analysis with previously published HCV-E sequences was 85 and 77 %, respectively. The B-cell epitope CFTPSPVVV at position 203 and the T-cell epitope ALSTGLIHL at position 380 were found to be highly conserved among all HCV genotypes. Both ELISA and Western blotting experiments on crude and purified recombinant HCV envelope proteins using mouse antisera raised using the HCV-E mammalian expression construct confirmed the specific antigenicity of the expressed protein. The antibodies raised in mice using the HCV-E-encoding construct could efficiently capture circulating antigens in patients’ sera with good sensitivity that correlated with liver enzyme levels (r = 0.4052, P < 0.0001 for ALT; r = −0.5439, P = 0.0019 for AST). Moreover, combining the HCV-E-encoding construct with extracts prepared from Echinacea purpurea and Nigella sativa prior to immunizing mice significantly (P < 0.05) increased both the humoral (14.9- to 20-fold increase in antibodies) and the cellular (CD4+ and cytotoxic CD8+- T lymphocytes) responses compared to mice that received the DNA construct alone or PBS-treated mice. Both recombinant HCV-E protein preparations and antibodies raised using the HCV-E-encoding mammalian expression construct represent useful diagnostic tools that can report on active HCV infection. Also, the immunostimulatory effects induced by the two plant extracts used at the cellular and humoral level highlight the potential of natural products for inducing protection against HCV infection. The neutralizing capacity of the induced antibodies is a subject of future investigations. Furthermore, the predicted B- and T-cell epitopes may be useful for tailoring future diagnostics and candidate vaccines against various HCV genotypes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. WHO (2014) WHO fact sheet: HCV vaccines number 164. http://www.who.int/mediacentre/factsheets/fs164/en/ Updated April 2014

  2. Abdelwahab SF, Hashem M, Galal I, Sobhy M, Abdel-Ghaffar TS, Galal G, Mikhail N, El-Kamary SS, Waked I, Strickland GT (2013) Incidence of hepatitis C virus infection among Egyptian healthcare workers at high risk of infection. J Clin Virol 57(1):24–28

    Article  PubMed  Google Scholar 

  3. Centers of Disease Control and Prevention (2012) CDC health information for international travel. morbidity and mortalityweekly report (MMWR) (RR04), vol 61. Oxford University Press, New York, pp 1–18

    Google Scholar 

  4. Pileri P, Uematsu Y, Campagnoli S, Galli G, Falugi F, Petracca R, Weiner AJ, Houghton M, Rosa D, Grandi G, Abrignani S (1998) Binding of hepatitis C virus to CD81. Science 282:938–941

    Article  CAS  PubMed  Google Scholar 

  5. Scarselli E, Ansuini H, Cerino R, Roccasecca RM, Acali S, Filocamo G, Traboni C, Nicosia A, Cortese R, Vitelli A (2002) The human scavenger receptor class B type I is a novel candidate receptor for the hepatitis C virus. EMBO J 21:5017–5025

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  6. Ploss A, Evans MJ, Gaysinskaya VA, Panis M, You H, de Jong Y, Rice CM (2009) Human occludin is a hepatitis C virus entry factor required for infection of mouse cells. Nature 457:882–886

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  7. Evans MJ, von Hahn T, Tscherne DM, Syder AJ, Panis M, Wolk B, Hatziioannou T, McKeating JA, Bieniasz PD, Rice CM (2007) Claudin-1 is a hepatitis C virus co-receptor required for a late step in entry. Nature 446:801–805

    Article  CAS  PubMed  Google Scholar 

  8. Pantua H, Diao J, Ultsch M, Hazen M, Mathieu M, McCutcheon K, Takeda K, Date S, Cheung TK, Phung Q, Hass P, Arnott D, Hongo JA, Matthews DJ, Brown A, Patel AH, Kelley RF, Eigenbrot C, Kapadia SB (2013) Glycan shifting on hepatitis c virus (HCV) E2 glycoprotein is a mechanism for escape from broadly neutralizing antibodies. J Mol Biol 425((11, 12)):1899–1914

    Article  CAS  PubMed  Google Scholar 

  9. Zubkova I, Duan H, Wells F, Mostowski H, Chang E, Pirollo K, Krawczynski K, Lanford R, Major M (2014) Hepatitis C virus clearance correlates with HLA-DR expression on proliferating CD8+ T cells in immune primed chimpanzees. Hepatology 59(3):803–813

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  10. Xue J, Zhu H, Chen Z (2014) Therapeutic vaccines against hepatitis C virus. Infect Genet Evolut 22:120–129

    Article  CAS  Google Scholar 

  11. Houghton M, Abrignani S (2005) Prospects for a vaccine against the hepatitis C virus. Nature 436(7053):961–966

    Article  CAS  PubMed  Google Scholar 

  12. Major ME (2009) Prophylactic and therapeutic vaccination against hepatitis C virus (HCV): developments and future perspectives. Viruses 1(2):144–165

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  13. Coates S, Choo Q L, Kuo G, Crawford K, Dong C, Wininger M, Weiner AJ, Berger K, Wong S, Ralston R, Morandi M, Pileri P, Rosa D, Muchmore E, Mahoney J, Brasky KM, Purcell RH, Abrignani S and Houghton M (2005). Protection of chimpanzees against heterologous 1a viral challenge using a gpE1/gpE2 heterodimer vaccine. In: Jilbert AR, Grgacic E VL, Vickery K, Burrell CJ, Cossart YE (eds) Proceedings of the 11th international symposium on viral hepatitis and liver disease. pp 118–123 (Australian Center for Hepatitis Virology)

  14. Reyes–del Valle J, de la Fuente C, Turner MA, Springfeld C, Apte-Sengupta S, Frenzke ME, Forest A, Whidby J, Marcotrigiano J, Rice CM, Cattaneo R (2012) Broadly neutralizing immune responses against hepatitis C virus induced by vectored measles viruses and a recombinant envelope protein booster. J Virol 86(21):11558–11566

    Article  PubMed Central  PubMed  Google Scholar 

  15. Martinez-Donato G, Amador-Cañizares Y, Alvarez-Lajonchere L, Guerra I, Pérez A, Dubuisson J, Wychowsk C, Musacchio A, Aguilar D, Dueñas-Carrera S (2014) Neutralizing antibodies and broad functional T cell immune response following immunization with hepatitis C virus proteins-based vaccine formulation. Vaccine 32(15):1720–1726

    Article  CAS  PubMed  Google Scholar 

  16. Firbas C, Jilma B, Tauber E, Buerger V, Jelovcan S, Lingnau K, Buschle M, Frisch J, Klade CS (2006) Immunogenicity and safety of a novel therapeutic hepatitis C virus (HCV) peptide vaccine: a randomized, placebo controlled trial for dose optimization in 128 healthy subjects. Vaccine 24(20):4343–4353

    Article  CAS  PubMed  Google Scholar 

  17. Vitti A, Nuzzaci M, Condelli V, Piazzolla P (2014) Simulated digestion for testing the stability of edible vaccine based on cucumber mosaic virus (CMV) chimeric particle display hepatitis C virus (HCV) peptide. In: virus hybrids as nanomaterials. Humana Press, pp 41–56

  18. Moser C, Müller M, Kaeser MD, Weydemann U, Amacker M (2013) Influenza virosomes as vaccine adjuvant and carrier system. Expert Rev Vaccines 12(7):779–791

    Article  CAS  PubMed  Google Scholar 

  19. Kushnir N, Streatfield SJ, Yusibov V (2012) Virus-like particles as a highly efficient vaccine platform: diversity of targets and production systems and advances in clinical development. Vaccine 31(1):58–83

    Article  CAS  PubMed  Google Scholar 

  20. Garber DA, O’Mara LA, Zhao J, Gangadhara S, An I, Feinberg MB (2009) Expanding the repertoire of modified vaccinia Ankara-based vaccine vectors via genetic complementation strategies. PLoS One 4(5):e5445

    Article  PubMed Central  PubMed  Google Scholar 

  21. Verheust C, Goossens M, Pauwels K, Breyer D (2012) Biosafety aspects of modified vaccinia virus Ankara (MVA)-based vectors used for gene therapy or vaccination. Vaccine 30(16):2623–2632

    Article  CAS  PubMed  Google Scholar 

  22. Randianarison V, Perricaudet M (1995) Recombinant adenoviruses as vaccines. Biologicals 23(2):145–157

    Article  Google Scholar 

  23. Wen B, Deng Y, Chen H, Guan J, Chuai X, Ruan L, Kong W, Tan W (2013) The novel replication-defective vaccinia virus (Tiantan Strain)—based hepatitis C virus vaccine induces robust immunity in macaques. Mol Ther 21(9):1787–1795

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  24. Dueñas-Carrera S (2004) DNA vaccination against hepatitis C. Curr Opin Mol Ther 6(2):146–150

    PubMed  Google Scholar 

  25. Weiland O, Ahlén G, Diepolder H, Jung MC, Levander S, Fons M, Mathiesen I, Sardesai NY, Vahlne A, Frelin L, Sällberg M (2013) Therapeutic DNA vaccination using in vivo electroporation followed by standard of care therapy in patients with genotype 1 chronic hepatitis C. Mol Ther 21(9):1796–1805

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  26. De Gregorio E, Caproni E, Ulmer JB (2013) Vaccine adjuvants: mode of action. Front Immunol 4:214

    Article  PubMed Central  PubMed  Google Scholar 

  27. Wu JM, Chen H, Sheng ZY, Wang J, Fan DY, Gao N, An J (2012) The adjuvant effect of granulocyte macrophage colony stimulating factor (GM-CSF) in dengue virus and hepatitis C virus DNA vaccines. Bing Du Xue Bao 28(3):207–212

    CAS  PubMed  Google Scholar 

  28. Naderi M, Saeedi A, Moradi A, Kleshadi M, Zolfaghari MR, Gorji A, Ghaemi A (2013) Interleukin-12 as a genetic adjuvant enhances hepatitis C virus NS3 DNA vaccine immunogenicity. Virol Sin 28(3):167–173

    Article  CAS  PubMed  Google Scholar 

  29. Hartoonian C, Ebtekar M, Soleimanjahi H, Karami A, Mahdavi M, Rastgoo N, Azadmanesh K (2009) Effect of immunological adjuvants: GM-CSF (granulocyte-monocyte colony stimulating factor) and IL-23 (interleukin-23) on immune responses generated against hepatitis C virus core DNA vaccine. Cytokine 46(1):43–50

    Article  CAS  PubMed  Google Scholar 

  30. Lin Y, Kwon T, Polo J, Zhu YF, Coates S, Crawford K, Dong C, Wininger M, Hall J, Selby M, Coit D, Medina-Selby A, McCoin C, Ng P, Drane D, Chien D, Han J, Vajdy M, Houghton M (2008) Induction of broad CD4+ and CD8+ T-cell responses and cross-neutralizing antibodies against hepatitis C virus by vaccination with Th1-adjuvanted polypeptides followed by defective alphaviral particles expressing envelope glycoproteins gpE1 and gpE2 and nonstructural proteins 3, 4, and 5. J Virol 82(15):7492–7503

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  31. Naarding MA, Falkowska E, Xiao H, Dragic T (2011) Hepatitis C virus soluble E2 in combination with QuilA and CpG ODN induces neutralizing antibodies in mice. Vaccine 29(16):2910–2917

    Article  CAS  PubMed  Google Scholar 

  32. Wedemeyer H, Gagneten S, Davis A, Bartenschlager R, Feinstone S, Rehermann B (2001) Oral immunization with HCV NS3 transformed Salmonella: induction of HCV specific CTL in a transgenic mouse model. Gastroenterology 12(5):1158–1166

    Article  Google Scholar 

  33. Cao J, Chen Z, Ren Y, Luo Y, Cao M, Lu W, Zhao P, Qi Z (2011) Oral immunization with attenuated Salmonella carrying a co-expression plasmid encoding the core and E2 proteins of hepatitis C virus capable of inducing cellular immune responses and neutralizing antibodies in mice. Vaccine 29(20):3714–3723

    Article  CAS  PubMed  Google Scholar 

  34. Qiu Q, Wang RY, Jiao X, Jin B, Sugauchi F, Grandinetti T, Alter HJ, Shih JW (2008) Induction of multispecific Th-1 type immune response against HCV in mice by protein immunization using CpG and Montanide ISA 720 as adjuvants. Vaccine 26(43):5527–5534

    Article  CAS  PubMed  Google Scholar 

  35. O’Hagan DT, Singh M, Dong C, Ugozzoli M, Berger K, Glazer E, Selby M, Wininger M, Ng P, Crawford K, Paliard X, Coates S, Houghton M (2004) Cationic microparticles are a potent delivery system for a HCV DNA vaccine. Vaccine 23(5):672–680

    Article  PubMed  Google Scholar 

  36. Ma X, Forns X, Gutierrez R, Mushahwar IK, Wu T, Payette PJ, Bukh J, Purcell RH, Davis HL (2002) DNA-based vaccination against hepatitis C virus (HCV): effect of expressing different forms of HCV E2 protein and use of CpG-optimized vectors in mice. Vaccine 20(27–28):3263–3271

    Article  CAS  PubMed  Google Scholar 

  37. Bode C, Zhao G, Steinhagen F, Kinjo T, Klinman DM (2011) CpG DNA as a vaccine adjuvant. Expert Rev Vaccines 10(4):499–511

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  38. Licciardi PV, Underwood JR (2011) Plant-derived medicines: a novel class of immunological adjuvants. Int Immunopharmacol 11(3):390–398

    Article  CAS  PubMed  Google Scholar 

  39. Mishima S, Saito K, Maruyama H, Inoue M, Yamashita T, Ishida T, Gu Y (2004) Antioxidant and immuno-enhancing effects of Echinacea purpurea. Biol Pharm Bull 27(7):1004–1009

    Article  CAS  PubMed  Google Scholar 

  40. Assayed ME (2010) Radioprotective effects of black seed (Nigella sativa) oil against hemopoietic damage and immunosuppression in gamma-irradiated rats. Immunopharmacol Immunotoxicol 32(2):284–296

    Article  PubMed  Google Scholar 

  41. Wilkins MR, Gasteiger E, Bairoch A, Sanchez JC, Williams KL, Appel RD, Hochstrasser DF (1999) Protein identification and analysis tools in the ExPASy server. Methods Mol Biol 112:531–552

    CAS  PubMed  Google Scholar 

  42. Möller S, Croning MDR, Apweiler R (2001) Evaluation of methods for the prediction of membrane spanning regions. Bioinformatics 17:646–653

    Article  PubMed  Google Scholar 

  43. Rost B (1996) PHD: predicting one-dimensional protein structure by profile-based neural networks. Methods Enzymol 266:525–539

    Article  CAS  PubMed  Google Scholar 

  44. McGuffin LJ, Bryson K, Jones DT (2000) The PSIPRED protein structure prediction server. Bioinformatics 16:404–405

    Article  CAS  PubMed  Google Scholar 

  45. Guex N, Peitsch MC (1997) SWISS-MODEL and the Swiss-Pdb Viewer: an environment for comparative protein modeling. Electrophoresis 18:2714–2723

    Article  CAS  PubMed  Google Scholar 

  46. Laskowski RA, MacArthur MW, Moss DS, Thornton JM (1993) PROCHECK - a program to check the stereochemical quality of protein structures. J App Cryst 26(2):283–291

    Article  CAS  Google Scholar 

  47. Vriend G (1990) WHAT IF: a molecular modeling and drug design program. J Mol Graph 8:52–56

    Article  CAS  PubMed  Google Scholar 

  48. Wiederstein M, Sippl MJ (2007) ProSA-web: interactive web service for the recognition of errors in three-dimensional structures of proteins. Nucleic Acids Res 35((Web Server issue)):W407–W410

    Article  PubMed Central  PubMed  Google Scholar 

  49. EL-Manzalawy Y, Dobbs D, Honavar V (2008) Prediction of linear B-cell epitopes using string kernels. J Mol Recognit 21(4):243–255

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  50. Kringelum JV, Lundegaard C, Lund O, Nielsen M (2012) Reliable B cell epitope predictions: impacts of method development and improved benchmarking. PLoS Comput Biol 8(12):e1002829

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  51. Doytchinova IA, Guan P, Flower DR (2006) EpiJen: a server for multistep T cell epitope prediction. BMC Bioinform 7:131

    Article  Google Scholar 

  52. Doytchinova IA, Flower DR (2007) VaxiJen: a server for prediction of protective antigens, tumor antigens and subunit vaccines. BMC Bioinform 8:4

    Article  Google Scholar 

  53. Vita R, Zarebski L, Greenbaum JA, Emami H, Hoof I, Salimi N, Damle R, Sette A, Peters B (2010) The immune epitope database 2.0. Nucleic Acids Res 38((Database issue)):D854–D862

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  54. Bahgat MM, Chlichlia K, Schirrmacher V, Ruppel A (2002) Antibodies induced in mice by a DNA-construct coding for the elastase of Schistosoma mansoni recognize the enzyme in secretions and preacetabular glands of cercariae. Parasitology 124:301–306

    Article  CAS  PubMed  Google Scholar 

  55. Towbin H, Staehelin T, Godon L (1979) Electrophoresis transfer of protein from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci USA 76:4350–4354

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  56. Engvall E, Perlmann P (1971) Enzyme-linked immunosorbent assay (ELISA). Quantitative assay of immunoglobulin G. Immunochem 8(9):871–874

    Article  CAS  Google Scholar 

  57. Maghraby AS (1989) Effect of bilharcid on the immune system of healthy and Schistosoma mansoni infected mice. M.Sc. Thesis, Faculty of Science, Cairo University

  58. Lock RJ, Unsworth DJ (2000) Measurement of immune complexes is not useful in routine clinical practice. Ann Clin Biochem 37:253–261

    Article  CAS  PubMed  Google Scholar 

  59. Maghraby AS, Bahgat MM (2004) Immunostimulatory effect of coumarin derivatives before and after infection of mice with the parasite Schistosoma mansoni. Arzneimittelforschung 54(9):545–550

    PubMed  Google Scholar 

  60. Lavillette D, Tarr AW, Voisset C, Donot P, Bartosch B, Bain C, Patel AH, Dubuisson J, Ball JK, Cosset FL (2005) Characterization of host-range and cell entry properties of the major genotypes and subtypes of hepatitis C virus. Hepatology 41(2):265–274

    Article  PubMed  Google Scholar 

  61. Liu J, Kong Y, Zhu L, Wang Y, Li G (2002) High-level expression of the C-terminal hydrophobic region of HCV E2 protein ectodomain in E. coli. Virus Genes 25(1):5–13

    Article  CAS  PubMed  Google Scholar 

  62. Guan J, Wen B, Deng Y, Zhang K, Chen H, Wu X, Ruan L, Tan W (2011) Effect of route of delivery on heterologous protection against HCV induced by an adenovirus vector carrying HCV structural genes. Virol J 8:506

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  63. Liu J, Zhu L, Zhang X, Lu M, Kong Y, Wang Y, Li G (2001) Expression, purification, immunological characterization and application of Escherichia coli-derived hepatitis C virus E2 proteins. Biotechnol Appl Biochem 34(2):109–119

    Article  PubMed  Google Scholar 

  64. Beld M, Penning M, McMorrow M, Gorgels J, Van den Hoek A, Goudsmit J (1998) Different hepatitis C virus (HCV) RNA load profiles following seroconversion among injecting drug users without correlation with HCV genotype and serum alanine aminotransferase levels. J Clin Microbiol 36:872–877

    PubMed Central  CAS  PubMed  Google Scholar 

  65. El-Awady MK, El-Demellawy MA, Khalil SB, Galal D, Goueli SA (2002) Synthetic peptide-based immunoassay as a supplemental test for HCV infection. Clin Chim Acta 325(1–2):39–46

    Article  CAS  PubMed  Google Scholar 

  66. El-Awady MK, Tabll AA, El-Abd YS, Yousif H, Hegab M, Reda M, El Shenawy R, Moustafa RI, Degheidy N, El-Din NG (2009) Conserved peptides within the E2 region of hepatitis C virus induce humoral and cellular responses in goats. Virol J 6:66–75

    Article  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgements

The authors acknowledge the National Research Centre (NRC) of Egypt for providing all needed facilities and logistics for the work. We are also grateful to Prof. Dr. Sohair Fawzy and Dr. Hossam Eid Gewaid for providing the HCV patients’ sera. This work was supported by several in-house grants provided by the NRC to Amany S. Maghraby and Mahmoud M. Bahgat, and by an annual funding from the NRC for the PhD work of Heba Shawky.

Author information

Authors and Affiliations

  1. The Immunology and Infectious Diseases Laboratory, Therapeutic Chemistry Department, The Center of Excellence for Advanced Sciences, The National Research Centre, Dokki, Giza, 12622, Egypt

    Heba Shawky, Amany S. Maghraby, Azza Arafa & Mahmoud M. Bahgat

  2. Vaccines Laboratory, Plant Biotechnology Department, Center of Excellence for Advanced Sciences, The National Research Centre, Dokki, Giza, 12622, Egypt

    Mohei El-Din Solliman

  3. Botany Department Women Collage for Arts, Science and Education, Ain- Shams University, Cairo, Egypt

    Mehreshan T. El-Mokadem

  4. Microbiology and Immunity Department, Faculty of Medicine, Al-Azhar University, Cairo, Egypt

    Mohamed M. Sherif

  5. Research Group Biomarkers in Infection and Immunity, Institute for Experimental Infection Research, TWINCORE, Centre for Clinical and Experimental Infection Research, Feodor-Lynen-Straße 7-9, 30625, Hannover, Germany

    Mahmoud M. Bahgat

Authors
  1. Heba Shawky
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Amany S. Maghraby
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mohei El-Din Solliman
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mehreshan T. El-Mokadem
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mohamed M. Sherif
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Azza Arafa
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Mahmoud M. Bahgat
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mahmoud M. Bahgat.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (PDF 90 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Shawky, H., Maghraby, A.S., Solliman, M.ED. et al. Expression, immunogenicity and diagnostic value of envelope proteins from an Egyptian hepatitis C virus isolate. Arch Virol 160, 945–958 (2015). https://doi.org/10.1007/s00705-015-2334-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00705-015-2334-1

Keywords

Search

Navigation