Skip to main content
Top
Published in: Virology Journal 1/2009

Open Access 01-12-2009 | Research

Sialylated glycans as receptor and inhibitor of enterovirus 71 infection to DLD-1 intestinal cells

Authors: Betsy Yang, Hau Chuang, Kuender D Yang

Published in: Virology Journal | Issue 1/2009

Login to get access

Abstract

Background

Many viruses recognize specific sugar residues, particularly sulfated or sialylated glycans, as the infection receptors. A change of sialic acid (2-6)-linked galactose (SA-α2,6Gal) to SA-α2,3Gal determines the receptor for avian flu infection. The receptor for enterovirus 71 (EV71) infection that frequently causes fatal encephalitis in Asian children remains unclear. Currently, there is no effective vaccine or anti-virus agent for EV71 infection. Using DLD-1 intestinal cells, this study investigated whether SA-linked glycan on DLD-1 intestinal cells was a receptor for EV71, and whether natural SA-linked sugars from human milk could block EV71 infection.

Results

EV71 specifically infected DLD-1 intestinal cells but not K562 myeloid cells. Depletion of O-linked glycans or glycolipids, but not N-linked glycans, significantly decreased EV71 infection of DLD-1 cells. Pretreatment of DLD-1 cells with sialidase (10 mU, 2 hours) significantly reduced 20-fold EV71 replication (p < 0.01). Taken together, these results suggest that SA-linked O-glycans and glycolipids, but not N-glycans, on DLD-1 cells were responsible for EV71 infection. Purified SA-α2,3Gal and SA-α2,6Gal from human milk significantly inhibited EV71 infection of DLD-1 cells, indicating terminal SA-linked glycans could be receptors and inhibitors of EV71 infection.

Conclusion

This is the first in the literature to demonstrate that EV71 uses SA-linked glycans as receptors for infection, and natural SA-linked glycans from human milk can protect intestinal cells from EV71 infection. Further studies will test how a SA-containing glycan can prevent EV71 in the future.
Appendix
Available only for authorised users
Literature
1.
go back to reference Suzuki Y: The highly pathogenic avian influenza H5N1-initial molecular signals for the next influenza pandemic. Chang Gung Med J 2009, 32: 258-263.PubMed Suzuki Y: The highly pathogenic avian influenza H5N1-initial molecular signals for the next influenza pandemic. Chang Gung Med J 2009, 32: 258-263.PubMed
2.
go back to reference Chang LY, Huang LM, Gau SS, Wu YY, Hsia SH, Fan TY, Lin KL, Huang YC, Lu CY, Lin TY: Neurodevelopment and cognition in children after enterovirus 71 infection. N Engl J Med 2007, 356: 1226-1234. 10.1056/NEJMoa065954CrossRefPubMed Chang LY, Huang LM, Gau SS, Wu YY, Hsia SH, Fan TY, Lin KL, Huang YC, Lu CY, Lin TY: Neurodevelopment and cognition in children after enterovirus 71 infection. N Engl J Med 2007, 356: 1226-1234. 10.1056/NEJMoa065954CrossRefPubMed
3.
go back to reference Chang LY: Enterovirus 71 in Taiwan. Pediatr Neonatol 2008, 49: 103-12. 10.1016/S1875-9572(08)60023-6CrossRefPubMed Chang LY: Enterovirus 71 in Taiwan. Pediatr Neonatol 2008, 49: 103-12. 10.1016/S1875-9572(08)60023-6CrossRefPubMed
4.
go back to reference Ang LW, Koh BK, Chan KP, Chua LT, James L, Goh KT: Epidemiology and control of hand, foot and mouth disease in Singapore, 2001-2007. Ann Acad Med Singapore 2009, 38: 106-112.PubMed Ang LW, Koh BK, Chan KP, Chua LT, James L, Goh KT: Epidemiology and control of hand, foot and mouth disease in Singapore, 2001-2007. Ann Acad Med Singapore 2009, 38: 106-112.PubMed
5.
go back to reference Ortner B, Huang CW, Schmid D, Mutz I, Wewalka G, Allerberger F, Yang JY, Huemer HP: Epidemiology of enterovirus types causing neurological disease in Austria 1999-2007: detection of clusters of echovirus 30 and enterovirus 71 and analysis of prevalent genotypes. J Med Virol 2009, 81: 317-324. 10.1002/jmv.21374CrossRefPubMed Ortner B, Huang CW, Schmid D, Mutz I, Wewalka G, Allerberger F, Yang JY, Huemer HP: Epidemiology of enterovirus types causing neurological disease in Austria 1999-2007: detection of clusters of echovirus 30 and enterovirus 71 and analysis of prevalent genotypes. J Med Virol 2009, 81: 317-324. 10.1002/jmv.21374CrossRefPubMed
6.
go back to reference Yang KD, Yang MY, Li CC, Lin SF, Chong MC, Wang CL, Chen RF, Lin TY: Altered cellular but not humoral reactions in children with complicated enterovirus 71 infections in Taiwan. J Infect Dis 2001, 183: 850-856. 10.1086/319255CrossRefPubMed Yang KD, Yang MY, Li CC, Lin SF, Chong MC, Wang CL, Chen RF, Lin TY: Altered cellular but not humoral reactions in children with complicated enterovirus 71 infections in Taiwan. J Infect Dis 2001, 183: 850-856. 10.1086/319255CrossRefPubMed
7.
go back to reference Varki NM, Varki A: Diversity in cell surface sialic acid presentations: implications for biology and disease. Lab Invest 2007, 87: 851-857. 10.1038/labinvest.3700656CrossRefPubMed Varki NM, Varki A: Diversity in cell surface sialic acid presentations: implications for biology and disease. Lab Invest 2007, 87: 851-857. 10.1038/labinvest.3700656CrossRefPubMed
8.
go back to reference Nilsson EC, Jamshidi F, Johansson SM, Oberste MS, Arnberg N: Sialic acid is a cellular receptor for coxackievirus A24 vairant, an emerging virus with pandemic potential. J Virol 2008, 82: 3061-3068. 10.1128/JVI.02470-07PubMedCentralCrossRefPubMed Nilsson EC, Jamshidi F, Johansson SM, Oberste MS, Arnberg N: Sialic acid is a cellular receptor for coxackievirus A24 vairant, an emerging virus with pandemic potential. J Virol 2008, 82: 3061-3068. 10.1128/JVI.02470-07PubMedCentralCrossRefPubMed
9.
go back to reference Schnabl KL, Field C, Clandinin MT: Ganglioside composition of differentiated Caco-2 cells resembles human colostrum and neonatal rat intestine. Br J Nutr 2008, 20: 1-7. Schnabl KL, Field C, Clandinin MT: Ganglioside composition of differentiated Caco-2 cells resembles human colostrum and neonatal rat intestine. Br J Nutr 2008, 20: 1-7.
10.
go back to reference 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: 794-797. 10.1038/nm.1961CrossRefPubMed 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: 794-797. 10.1038/nm.1961CrossRefPubMed
11.
go back to reference Li CC, Yang MY, Chen RF, Lin TY, Tsao KC, Ning HC, Liu HC, Lin SF, Yeh WT, Chu YT, Yang KD: Clinical manifestations and laboratory assessment in an enterovirus 71 outbreak in southern Taiwan. Scan J Infect Dis 2002, 34: 104-109. 10.1080/00365540110077119CrossRef Li CC, Yang MY, Chen RF, Lin TY, Tsao KC, Ning HC, Liu HC, Lin SF, Yeh WT, Chu YT, Yang KD: Clinical manifestations and laboratory assessment in an enterovirus 71 outbreak in southern Taiwan. Scan J Infect Dis 2002, 34: 104-109. 10.1080/00365540110077119CrossRef
12.
go back to reference Balzarini J: Targeting the glycans of glycoproteins: a novel paradigm for antiviral therapy. Nat Rev Microbiol 2007, 5: 583-597. 10.1038/nrmicro1707CrossRefPubMed Balzarini J: Targeting the glycans of glycoproteins: a novel paradigm for antiviral therapy. Nat Rev Microbiol 2007, 5: 583-597. 10.1038/nrmicro1707CrossRefPubMed
13.
go back to reference Weng TY, Chen LC, Shyu HW, Chen SH, Wang JR, Yu CK, Lei HY, Yeh TM: Lactoferrin inhibits enterovirus 71 infection by binding to VP1 protein and host cells. Antivirus Res 2005, 67: 31-37. 10.1016/j.antiviral.2005.03.005CrossRef Weng TY, Chen LC, Shyu HW, Chen SH, Wang JR, Yu CK, Lei HY, Yeh TM: Lactoferrin inhibits enterovirus 71 infection by binding to VP1 protein and host cells. Antivirus Res 2005, 67: 31-37. 10.1016/j.antiviral.2005.03.005CrossRef
Metadata
Title
Sialylated glycans as receptor and inhibitor of enterovirus 71 infection to DLD-1 intestinal cells
Authors
Betsy Yang
Hau Chuang
Kuender D Yang
Publication date
01-12-2009
Publisher
BioMed Central
Published in
Virology Journal / Issue 1/2009
Electronic ISSN: 1743-422X
DOI
https://doi.org/10.1186/1743-422X-6-141

Other articles of this Issue 1/2009

Virology Journal 1/2009 Go to the issue