Skip to main content

Advertisement

SpringerLink
Log in

Impact of hepatitis B virus genotype F on in vitro diagnosis: detection efficiency of HBsAg from Amerindian subgenotypes F1b and F4

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

Abstract

The influence of the high genetic variability of hepatitis B virus (HBV) on the sensitivity of serological assays has received little attention so far. A major source of variability is related to viral genotypes and subgenotypes. Their possible influence on diagnosis and prophylaxis is poorly known and has mostly been evaluated for genotypes A, B, C and D. Robust data showing the detection efficiency of HBsAg from genotype F is lacking. This study examined the effect of virus-like particles containing HBsAg from genotypes A and F (particularly, F1b and F4) produced in Pichia pastoris in relation to the anti-HBs antibodies used in the immunoassays for in vitro diagnosis and compared it with that exerted by the G145R S-escape mutant. The results showed that HBsAg detection rates for subgenotypes F1b and F4 differed significantly from those obtained for genotype A and that subgenotype F1b had a major impact on the sensitivity of the immunoassays tested. Prediction of the tertiary structure of subgenotypes F1b and F4 revealed changes inside and outside the major hydrophilic region (aa 101-160) of the HBsAg compared to genotype A and the G145R variant. A phosphorylation site (target for protein kinase C) produced by the G145R substitution might prevent recognition by anti-HBs antibodies. In conclusion, the use of different genotypes or variants for diagnosis could improve the rate of detection of HBV infection. The incorporation of a genotype-F-derived HBsAg vaccine in areas where this genotype is endemic should be evaluated, since this might also affect vaccination efficacy.

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

Similar content being viewed by others

References

  1. WHO (2017) Hepatitis B. World Health Organization Fact sheet N°204. http://www.who.int/mediacentre/factsheets/fs204/en. Accessed 9 Apr 2018

  2. Kramvis A (2014) Genotypes and genetic variability of hepatitis B virus. Intervirology 57:141–150. https://doi.org/10.1159/000360947

    Article  PubMed  Google Scholar 

  3. Lin CL, Kao JH (2017) Natural history of acute and chronic hepatitis B: the role of HBV genotypes and mutants. Best Pract Res Clin Gastroenterol 31:249–255. https://doi.org/10.1016/j.bpg.2017.04.010

    Article  CAS  PubMed  Google Scholar 

  4. Croagh CMN, Desmond PV, Bell SJ (2015) Genotypes and viral variants in chronic hepatitis B: a review of epidemiology and clinical relevance. World J Hepatol 7(3):289–303. https://doi.org/10.4254/wjh.v7.i3.289

    Article  PubMed  PubMed Central  Google Scholar 

  5. Pourkarim MR, Amini-Bavil-Olyaee S, Kurbanov F, Van Ranst M, Tacke F (2014) Molecular identification of hepatitis B virus genotypes/subgenotypes: revised classification hurdles and updated resolutions. World J Gastroenterol 20(23):7152–7168

    Article  PubMed  PubMed Central  Google Scholar 

  6. Alvarado-Mora MV, Rebello Pinho JR (2013) Distribution of HBV genotypes in Latin America. Antivir Ther 18:459–465. https://doi.org/10.3851/IMP2599

    Article  PubMed  Google Scholar 

  7. Sanchez-Tapias JM, Costa J, Mas A, Bruguera M, Rodes J (2002) Influence of hepatitis B virus genotype on the long-term outcome of chronic hepatitis B in Western patients. Gastroenterology 123:1848–1856

    Article  PubMed  Google Scholar 

  8. Livingston SE, Simonetti J, McMahn BJ, Bulkow LR, Hurlburt KJ, Homan CE, Snowball MM, Cagle HH, Williams JL, Chulanov VP (2007) Hepatitis B virus genotypes in Alaska Native people with hepatocellular carcinoma: preponderance of genotype F. J Infect Dis 195:5–11

    Article  CAS  PubMed  Google Scholar 

  9. Marciano S, Galdamo OA, Gadano AC (2013) HBV genotype F: Natural history and treatment. Antivir Ther 18:485–488. https://doi.org/10.3851/IMP2604

    Article  PubMed  Google Scholar 

  10. Cassidy A, Mossman S, De Ridder M, Leroux-Roels G (2011) Hepatitis B vaccine effectiveness in the face of global HBV genotype diversity. Expert Rev Vaccines 10(12):1709–1715. https://doi.org/10.1586/erv.11.151

    Article  CAS  PubMed  Google Scholar 

  11. Tacke F, Amini-Bavil-Olyaee S, Heim A, Luedde T, Manns MP, Trautwein C (2007) Acute hepatitis B virus infection by genotype F despite successful vaccination in an immune-competent German patient. J Clin Virol 38:353–357

    Article  CAS  PubMed  Google Scholar 

  12. O’Halloran JA, De Gascun CF, Dunford L, Carr MJ, Connell J, Howard R, Hall WW, Lambert JS (2011) Hepatitis B virus vaccine failure resulting in chronic hepatitis B infection. J Clin Virol 52:151–154. https://doi.org/10.1016/j.jcv.2011.06.020

    Article  PubMed  Google Scholar 

  13. Xiao A, Zhou X, Zhou L, Zhang Y (2006) Improvement of cell viability and hirudin production by ascorbic acid in Pichia pastoris fermentation. Appl Microbiol Biotechnol 72:837–844

    Article  CAS  PubMed  Google Scholar 

  14. Celik E, Calık P, Oliver S (2009) Fed-batch methanol feeding strategy for recombinant protein production by Pichia pastoris in the presence of co-substrate sorbitol. Yeast 26:473–484

    Article  CAS  PubMed  Google Scholar 

  15. Bhatacharya P, Pandey G, Mukherjee KJ (2007) Production and purification of recombinant human granulocyte-macrophage colony stimulating factor (GM-CSF) from high cell density cultures of Pichia pastoris. Bioprocess Biosyst Eng 30:305–312

    Article  CAS  PubMed  Google Scholar 

  16. Noseda DG, Recúpero MN, Blasco M, Ortiz GE, Galvagno MA (2013) Cloning, expression and optimized production in a bioreactor of bovine chymosin B in Pichia (Komagataella) pastoris under AOXI promoter. Protein Expr Purif 92:235–244. https://doi.org/10.1016/j.pep.2013.08.018

    Article  CAS  PubMed  Google Scholar 

  17. Noseda DG, Blasco M, Recúpero MN, Galvagno MA (2014) Bioprocess and downstream optimization of recombinant bovine chymosin B in Pichia (Komagataella) pastoris under methanol-inducible AOXI promoter. Protein Expr Purif 104:85–91. https://doi.org/10.1016/j.pep.2014.09.014

    Article  CAS  PubMed  Google Scholar 

  18. Bardiya N (2006) Expression in and purification of hepatitis B surface antigen (S-protein) from methylotrophic yeast Pichia pastoris. Anaerobe 12:194–203

    Article  CAS  PubMed  Google Scholar 

  19. Gurramkonda C, Zahid M, Nemani SK, Adnan A, Gudi SK, Ebensen T, Lünsdorf H, Guzmán CA, Rinas U (2013) Purification of hepatitis B surface antigen virus-like particles from recombinant Pichia pastoris and in vivo analysis of their immunogenic properties. J Chromatogr B Analyt Technol Biomed Life Sci 940:104–111. https://doi.org/10.1016/j.jchromb.2013.09.030

    Article  CAS  PubMed  Google Scholar 

  20. Peyret H (2015) A protocol for the gentle purification of virus like particles produced in plants. J Virol Methods 225:59–63. https://doi.org/10.1016/j.jviromet.2015.09.005

    Article  CAS  PubMed  Google Scholar 

  21. Drozdetskiy A, Cole C, Procter J, Barton GJ (2015) JPred4: a protein secondary structure prediction server. Nucleic Acids Res 43(W1):W389–W394. https://doi.org/10.1093/nar/gkv332

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Yang J, Yan R, Roy A, Xu D, Poisson J, Zhang Y (2015) The I-TASSER Suite: Protein structure and function prediction. Nat Methods 12:7–8. https://doi.org/10.1038/nmeth.3213

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Laskowski RA, MacArthur MW, Moss D, Thornton JM (1993) PROCHECK: a program to check the stereochemical quality of protein structures. J Appl Crystallogr 26:283–291

    Article  CAS  Google Scholar 

  24. Studer G, Biasini M, Schwede T (2014) Assessing the local structural quality of transmembrane protein models using statistical potentials (QMEANBrane). Bioinformatics 30(17):i505–i511. https://doi.org/10.1093/bioinformatics/btu457

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. 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:W407–W410

    Article  PubMed  PubMed Central  Google Scholar 

  26. Xu D, Zhang Y (2011) Improving the physical realism and structural accuracy of protein models by a two-step atomic-level energy minimization. Biophys J 101:2525–2534. https://doi.org/10.1016/j.bpj.2011.10.024

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Lomize MA, Pogozheva ID, Joo H, Mosberg HI, Lomize AL (2012) OPM database and PPM web server: resources for positioning of proteins in membranes. Nucleic Acids Res 40(Database issue):D370–D376. https://doi.org/10.1093/nar/gkr703

    Article  CAS  PubMed  Google Scholar 

  28. Holm L, Rosenström P (2010) Dali server: conservation mapping in 3D. Nucleic Acids Res 38:W545–W549. https://doi.org/10.1093/nar/gkq366

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM, Meng EC, Ferrin TE (2004) UCSF Chimera—a visualization system for exploratory research and analysis. J Comput Chem 25(13):1605–1612

    Article  CAS  PubMed  Google Scholar 

  30. Milhiet P-E, Dosset P, Godefroy C, Le Grimellec C, Guigner J-M, Larquet E, Ronzon F, Manin C (2011) Nanoscale topography of hepatitis B antigen particles by atomic force microscopy. Biochimie 93:254–259. https://doi.org/10.1016/j.biochi.2010.09.018

    Article  CAS  PubMed  Google Scholar 

  31. Lündsorf H, Gurramkonda C, Adnan A, Khanna N, Rinas U (2001) Virus-like particle production with yeast: ultrastructural and immunocytochemical insights into Pichia pastoris producing high levels of the hepatitis B surface antigen. Microb Cell Fact 10:48

    Google Scholar 

  32. Wampler DE, Lehman ED, Boger J, McAleer WJ, Scolnick EM (1985) Multiple chemical forms of hepatitis B surface antigen produced in yeast. Proc Natl Acad Sci USA 82:6830–6834

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Zhao Q, Wang Y, Freed D, Fu T-M, Gimenez JA, Sitrin RD, Washabaugh MW (2006) Maturation of recombinant hepatitis B virus surface antigen particles. Hum Vaccin 2(4):174–180

    Article  CAS  PubMed  Google Scholar 

  34. Zahid M, Lündsorf H, Rinas U (2015) Assessing stability and assembly of the hepatitis B surface antigen into virus-like particles during down-stream processing. Vaccine 33:3739–3745. https://doi.org/10.1016/j.vaccine.2015.05.066

    Article  CAS  PubMed  Google Scholar 

  35. Ottone S, Nguyen X, Bazin J, Bérard C, Jimenez S, Letourneur O (2007) Expression of hepatitis B surface antigen major subtypes in Pichia pastoris and purification for in vitro diagnosis. Protein Expr Purif 56:177–188

    Article  CAS  PubMed  Google Scholar 

  36. Gilbert RJ, Beales L, Blond D, Simon MN, Lin BY, Chisari FV, Stuart DI, Rowlands DJ (2005) Hepatitis B small surface antigen particles are octahedral. Proc Natl Acad Sci USA 102(41):14783–14788

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Olinger CM, Weber B, Otegbayo JA, Ammerlaan W, van der Taelem-Brulé N, Muller CP (2007) Hepatitis B virus genotype E surface antigen detection with different immunoassays and diagnostic impact of mutations in the preS/S gene. Med Microbiol Immunol 196:247–252

    Article  CAS  PubMed  Google Scholar 

  38. Araujo NM, Vianna COA, Morales MTB, Gomes SA (2009) Expression of hepatitis B virus surface antigen (HBsAg) from genotypes A, D and F and influence of amino acid variations related or not to genotypes on HBsAg detection. Braz J Infect Dis 13:266–271

    CAS  PubMed  Google Scholar 

  39. Scheiblauer H, El-Nageh M, Diaz S, Nick S, Zeichhardt H, Grunet H-P, Prince A (2010) Performance evaluation of70 hepatitis B virus (HBV) surface antigen (HBsAg) assays from around the world by a geographically diverse panel with an array of HBV genotypes and HBsAg subtypes. Vox Sang 98:403–414. https://doi.org/10.1111/j.1423-0410.2009.01272.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Hadiji-Abbes N, Mihoubi W, Martin M, Karakasyan-Dia C, Frikha F, Gergely C, Jouenne T, Gargouri A, Mokdad-Gargouri R (2015) Characterization of C69R variant HBsAg: effect on bindingto anti-HBs and the structure of virus-like particles. Arch Virol 160:2427–2433. https://doi.org/10.1007/s00705-015-2515-y

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

DGN, ADN, PDG, CSC and MLC are staff members of CONICET. MJL thanks CONICET for her doctoral scholarship.

Funding

This study was funded by the University of Buenos Aires (Grant UBACyT 20020130200222BA) and by the Agencia Nacional de Promoción Científica y Técnica (ANPCyT, Grant PICT 201-0206).

Author information

Authors and Affiliations

  1. CONICET, Instituto de Investigaciones en Microbiología y Parasitología Médica (IMPaM), Universidad de Buenos Aires, Buenos Aires, Argentina

    María J. Limeres & María L. Cuestas

  2. Instituto de Agrobiotecnología y Biología Molecular, INTA-CONICET, Buenos Aires, Argentina

    Evangelina R. Gomez

  3. Instituto de Investigaciones Biotecnológicas-Instituto Tecnológico de Chascomús (IIB-INTECH), Universidad Nacional de San Martín (UNSAM)-Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina

    Diego G. Noseda

  4. Departamento de Ciencia y Tecnología, Laboratorio de Ingeniería Genética y Biología Celular y Molecular, Área Virosis de Insectos (LIGBCM-AVI), Instituto de Microbiología Básica y Aplicada (IMBA), Universidad Nacional de Quilmes, Bernal, Provincia de Buenos Aires, Argentina

    Carolina S. Cerrudo & Pablo D. Ghiringhelli

  5. Facultad de Farmacia y Bioquímica, Instituto de Nanobiotecnología (NANOBIOTEC), Universidad de Buenos Aires, Buenos Aires, Argentina

    Alejandro D. Nusblat

Authors
  1. María J. Limeres
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Evangelina R. Gomez
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Diego G. Noseda
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Carolina S. Cerrudo
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Pablo D. Ghiringhelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Alejandro D. Nusblat
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. María L. Cuestas
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to María L. Cuestas.

Ethics declarations

Conflict of interest

The authors declare that they have no conflicts of interest regarding funding or other aspects of this manuscript.

Ethical approval

The study was approved by the institutional review committee at Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires (Ref. EXP- UBA N” 0051009/2016).

Additional information

Handling Editor: Zhongjie Shi.

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 18 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Limeres, M.J., Gomez, E.R., Noseda, D.G. et al. Impact of hepatitis B virus genotype F on in vitro diagnosis: detection efficiency of HBsAg from Amerindian subgenotypes F1b and F4. Arch Virol 164, 2297–2307 (2019). https://doi.org/10.1007/s00705-019-04332-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00705-019-04332-8

Search

Navigation