Skip to main content
Log in

Initial evidence on differences among Enterovirus 71, Coxsackievirus A16 and Coxsackievirus B4 in binding to cell surface heparan sulphate

  • Original Article
  • Published:
VirusDisease Aims and scope Submit manuscript

Abstract

Cell surface heparan sulphate (HS) mediates infection for many viruses from diverse families. We demonstrated significant antiviral potencies for a number of HS mimetics against a cloned strain of Enterovirus 71 (EV71) in a previous study. Thus, the involvement of HS in mediating viral infection of isolates of human enteroviruses was investigated in Vero and human neural cells in the present work. In both cell lines, heparin and pentosan polysulphate significantly inhibited both infection and attachment of low passage clinical isolates of EV71 and Coxsackievirus A16 (CVA16) but showed no affect on Coxsackievirus B4 (CVB4) (p < 0.05). In addition, enzymatic removal of cell surface HS by heparinase I prevented binding of the clinical EV71 by nearly 50 % but failed to significantly inhibit CVA16 or CVB4 binding in Vero cells. Overall, the findings of this study provides evidence that whilst highly sulphated domains of HS serve as an essential attachment co-receptor for EV71, HS might be used as an alternative attachment receptor by the other member of Human Enterovirus group A, CVA16. In addition, HS may not mediate early infection in CVB4.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Baranowski E, Sevilla N, Verdaguer N, Ruiz-Jarabo CM, Beck E, Domingo E. Multiple virulence determinants of foot-and-mouth disease virus in cell culture. J Virol. 1998;72:6362–72.

    CAS  PubMed Central  PubMed  Google Scholar 

  2. Bernard KA, Klimstra WB, Johnston RE. Mutations in the E2 glycoprotein of Venezuelan equine encephalitis virus confer heparan sulfate interaction, low morbidity, and rapid clearance from blood of mice. Virology. 2000;276:93–103.

    Article  CAS  PubMed  Google Scholar 

  3. De Logu A, Loy G, Pellerano ML, Bonsignore L, Schivo ML. Inactivation of HSV-1 and HSV-2 and prevention of cell-to-cell virus spread by Santolina insularis essential oil. Antiviral Res. 2000;48:177–85.

    Article  PubMed  Google Scholar 

  4. Ernst S, Langer R, Cooney CL, Sasisekharan R. Enzymatic degradation of glycosaminoglycans. Crit Rev Biochem Mol Biol. 1995;30:387–444.

    CAS  PubMed  Google Scholar 

  5. Escarmis C, Carrillo EC, Ferrer M, Arriaza JFG, Lopez N, Tami C, Verdaguer N, Domingo E, Franze-Fernandez MT. Rapid selection in modified BHK-21 cells of a foot-and-mouth disease virus variant showing alterations in cell tropism. J Virol. 1998;72:10171–9.

    CAS  PubMed Central  PubMed  Google Scholar 

  6. Escribano-Romero E, Jimenez-Clavero MA, Gomes P, Garcia-Ranea JA, Ley V. Heparan sulphate mediates swine vesicular disease virus attachment to the host cell. J Gen Virol. 2004;85:653–63.

    Article  CAS  PubMed  Google Scholar 

  7. Flynn SJ, Burgett BL, Stein DS, Wilkinson KS, Ryan P. The amino-terminal one-third of pseudorabies virus glycoprotein gIII contains a functional attachment domain, but this domain is not required for the efficient penetration of Vero cells. J Virol. 1993;67:2646–54.

    CAS  PubMed Central  PubMed  Google Scholar 

  8. Goodfellow IG, Sioofy AB, Powell RM, Evans DJ. Echoviruses bind heparan sulfate at the cell surface. J Virol. 2001;75:4918–21.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  9. Klimstra WB, Ryman KD, Johnston RE. Adaptation of Sindbis virus to BHK cells selects for use of heparan sulfate as an attachment receptor. J Virol. 1998;72:7357–66.

    CAS  PubMed Central  PubMed  Google Scholar 

  10. Leong JM, Wang H, Magoun L, Field JA, Morrissey PE, Robbins D, Tatro JB, Coburn J, Parveen N. Different classes of proteoglycans contribute to the attachment of Borrelia burgdorferi to cultured endothelial and brain cells. Infect Immun. 1998;66:994–9.

    CAS  PubMed Central  PubMed  Google Scholar 

  11. McLeish NG, Williams CH, Kaloudas D, Roivainen MR, Stanway G. Symmetry-related clustering of positive charges is a common mechanism for heparan sulfate binding in enteroviruses. J Virol. 2012;86:1113–70.

    Article  Google Scholar 

  12. Neff S, Sá-Carvalho D, Rieder E, Mason P, Blystone S, Brown E, Baxt B. Foot-and-mouth disease virus virulent for cattle utilizes the integrin αvβ3 as its receptor. J Virol. 1998;72:3587–94.

    CAS  PubMed Central  PubMed  Google Scholar 

  13. Nishimura Y, Shimojima M, Tano Y, Miyamura T, Wakita T, Shimizu H. Human P-selectin glycoprotein ligand-1 is a functional receptor for enterovirus 71. Nat Med. 2009;15:794–7.

    Article  CAS  PubMed  Google Scholar 

  14. Olofsson S, Bergström T. Glycoconjugate glycans as viral receptors. Ann Med. 2005;37:154–72.

    Article  CAS  PubMed  Google Scholar 

  15. Pourianfar HR, Javadi A, Grollo L. A colorimetric-based accurate method for the determination of Enterovirus 71 titer. Indian J Virol. 2012;23:303–10.

    Article  PubMed Central  PubMed  Google Scholar 

  16. Pourianfar HR, Poh CL, Fecondo J, Grollo L. In vitro evaluation of the antiviral activity of heparan sulphate mimetic compounds against Enterovirus 71. Virus Res. 2012;169:22–9.

    Article  CAS  PubMed  Google Scholar 

  17. Rabenstein DL. Heparin and heparan sulfate: structure and function. Nat Prod Rep. 2002;19:312–31.

    Article  CAS  PubMed  Google Scholar 

  18. Sa-Carvalho D, Rieder E, Baxt B, Rodarte R, Tanuri A, Mason P. Tissue culture adaptation of foot-and-mouth disease virus selects viruses that bind to heparin and are attenuated in cattle. J Virol. 1997;71:5115–23.

    CAS  PubMed Central  PubMed  Google Scholar 

  19. Schmidtke M, Schnittler U, Jahn B, Dahse HM, Stelzner A. A rapid assay for evaluation of antiviral activity against coxsackie virus B3, influenza virus A, and herpes simplex virus type 1. J Virol Methods. 2001;95:133–43.

    Article  CAS  PubMed  Google Scholar 

  20. Tan CW, Poh CL, Sam IC, Chan YF. Enterovirus 71 uses cell surface heparan sulfate glycosaminoglycan as an attachment receptor. J Virol. 2013;87:611–20.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  21. Vrublevskaya VV, Kornev AN, Smirnov SV, Morenkov OS. Cell-binding properties of glycoprotein B of Aujeszky’s disease virus. Virus Res. 2002;86:7–19.

    Article  CAS  PubMed  Google Scholar 

  22. Yamayoshi S, Yamashita Y, Li J, Hanagata N, Minowa T, Takemura T, Koike S. Scavenger receptor B2 is a cellular receptor for enterovirus 71. Nat Med. 2009;15:798–801.

    Article  CAS  PubMed  Google Scholar 

  23. Yang B, Chuang H, Yang KD. Sialylated glycans as receptor and inhibitor of enterovirus 71 infection to DLD-1 intestinal cells. Virol J. 2009;6:141.

    Article  PubMed Central  PubMed  Google Scholar 

  24. Zautner AE, Korner U, Henke A, Badorff C, Schmidtke M. Heparan sulfates and coxsackievirus–adenovirus receptor: each one mediates coxsackievirus B3 PD infection. J Virol. 2003;77:10071–7.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  25. Zhu W, Li J, Liang G. How does cellular heparan sulfate function in viral pathogenicity? Biomed Environ Sci. 2011;24:81–7.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study was part of the PhD project of HRP at Swinburne University of Technology, Melbourne, Australia. The authors wish to thank Professor Peter C. McMinn (Central Clinical School, University of Sydney, Australia) for providing the cloned EV71 virus and the cells. The Australian Centre for infectious disease is also appreciated for providing the clinical isolates of EV71, CVA16 and CVB4.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Lara Grollo.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Pourianfar, H.R., Kirk, K. & Grollo, L. Initial evidence on differences among Enterovirus 71, Coxsackievirus A16 and Coxsackievirus B4 in binding to cell surface heparan sulphate. VirusDis. 25, 277–284 (2014). https://doi.org/10.1007/s13337-013-0172-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13337-013-0172-x

Keywords

Navigation