Glycoconjugate Journal

, Volume 29, Issue 4, pp 211–220 | Cite as

Specific interaction of the envelope glycoproteins E1 and E2 with liver heparan sulfate involved in the tissue tropismatic infection by hepatitis C virus

  • Fumi Kobayashi
  • Shuhei YamadaEmail author
  • Shuhei Taguwa
  • Chikako Kataoka
  • Satomi Naito
  • Yoshiki Hama
  • Hideki Tani
  • Yoshiharu Matsuura
  • Kazuyuki SugaharaEmail author


The first step in the process of infections by the hepatitis C virus (HCV) is attachment to the host cell, which is assumed to be mediated by interaction of the envelope glycoproteins E1 and E2 with cell surface glycosaminoglycans. In this study, a variety of glycosaminoglycans, heparan sulfate (HS) from various bovine tissues as well as chondroitin sulfate (CS)/dermatan sulfate from bovine liver, were used to examine the direct interaction with recombinant E1 and E2 proteins. Intriguingly, among HS preparations from various bovine tissues, only liver HS strongly bound to both E1 and E2. Since HS from liver, which is the target tissue of HCV, contains highly sulfated structures compared to HS from other tissues, the present results suggest that HS-proteoglycan on the liver cell surface appears to be one of the molecules that define the liver-specific tissue tropism of HCV infection. The interaction assay with chemically modified heparin derivatives provided evidence that the binding of the viral proteins to heparin/HS is not only mediated by simple ionic interactions, but that the 6-O-sulfation and N-sulfation are important. Heparin oligosaccharides equal to or larger than 10-mer were required to inhibit the binding. Notably, a highly sulfated CS-E preparation from squid cartilage also strongly interacted with both viral proteins and inhibited the entry of pseudotype HCV into the target cells, suggesting that the highly sulfated CS-E might be useful as an anti-HCV drug.


Heparan sulfate Chondroitin sulfate Hepatitis C virus Glycosaminoglycan Tissue tropism 





completely desulfated and N-acetylated heparin


completely desulfated and N-sulfated heparin


N-desulfated and N-acetylated heparin


2-O-desulfated heparin


6-O-desulfated heparin


chondroitin sulfate


dermatan sulfate


enzyme-linked immunosorbent assay


fibroblast growth factor




hepatitis C virus


4-deoxy-α-L-threo-hex-4-enepyranosyluronic acid


high performance liquid chromatography


heparan sulfate




vesicular stomatitis virus











The authors thank Satoko Ueno, Naoko Shoji, and Machiko Tomimatsu for technical assistance. This work was supported in part by Grants-in-aid for Scientific Research C-21590057 (to S. Y.), Scientific Research (B) 23390016 (to K. S.), and the Matching Program for Innovations in Future Drug Discovery and Medical Care (to K. S.) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (MEXT).

Supplementary material

10719_2012_9388_MOESM1_ESM.pdf (296 kb)
Supplementary Data 1 (PDF 296 kb)
10719_2012_9388_MOESM2_ESM.pdf (130 kb)
Supplementary Data 2 (PDF 130 kb)


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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Fumi Kobayashi
    • 1
  • Shuhei Yamada
    • 1
    • 2
    • 4
    Email author
  • Shuhei Taguwa
    • 3
  • Chikako Kataoka
    • 3
  • Satomi Naito
    • 2
  • Yoshiki Hama
    • 1
  • Hideki Tani
    • 3
  • Yoshiharu Matsuura
    • 3
  • Kazuyuki Sugahara
    • 1
    • 2
    Email author
  1. 1.Laboratory of Proteoglycan Signaling and TherapeuticsHokkaido University Graduate School of Life ScienceSapporoJapan
  2. 2.Department of BiochemistryKobe Pharmaceutical UniversityHigashinada-kuJapan
  3. 3.Department of Molecular Virology, Research Institute for Microbial DiseasesOsaka UniversitySuita-shiJapan
  4. 4.Department of Pathobiochemistry, Faculty of PharmacyMeijo UniversityTempaku-kuJapan

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