Characterization of a heparan sulfate octasaccharide that binds to herpes simplex virus type 1 glycoprotein D

Jian Liu, Zach Shriver, R. Marshall Pope, Suzanne C. Thorp, Michael B Duncan, Ronald J. Copeland, Christina S. Raska, Keiichi Yoshida, Roselyn J. Eisenberg, Gary Cohen, Robert J. Linhardt, Ram Sasisekharan

Research output: Contribution to journalArticlepeer-review

157 Scopus citations

Abstract

Herpes simplex virus type 1 utilizes cell surface heparan sulfate as receptors to infect target cells. The unique heparan sulfate saccharide sequence offers the binding site for viral envelope proteins and plays critical roles in assisting viral infections. A specific 3-O-sulfated heparan sulfate is known to facilitate the entry of herpes simplex virus 1 into cells. The 3-O-sulfated heparan sulfate is generated by the heparan sulfate D-glucosaminyl-3-O-sulfotransferase isoform 3 (3-OST-3), and it provides binding sites for viral glycoprotein D (gD). Here, we report the purification and structural characterization of an oligosaccharide that binds to gD. The isolated gD-binding site is an octasaccharide, and has a binding affinity to gD around 18 μM, as determined by affinity coelectrophoresis. The octasaccharide was prepared and purified from a heparan sulfate oligosaccharide library that was modified by purified 3-OST-3 enzyme. The molecular mass of the isolated octasaccharide was determined using both nanoelectrospray ionization mass spectrometry and matrix-assisted laser desorption/ionization mass spectrometry. The results from the sequence analysis suggest that the structure of the octasaccharide is a heptasulfated octasaccharide. The proposed structure of the octasaccharide is ΔUA-GlcNS-IdoUA2S-GlcNAc-UA2S-GlcNS-IdoUA2S-GlcNH23S6S. Given that the binding of 3-O-sulfated heparan sulfate to gD can mediate viral entry, our results provide structural information about heparan sulfate-assisted viral entry.

Original languageEnglish (US)
Pages (from-to)33456-33467
Number of pages12
JournalJournal of Biological Chemistry
Volume277
Issue number36
DOIs
StatePublished - Sep 6 2002

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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