Biochem. J. (2005) 385
(451–459) (Printed in Great Britain)
Characterization of heparan sulphate 3-O-sulphotransferase isoform 6 and its role in assisting the entry of herpes simplex virus type 1
Ding XU*, Vaibhav TIWARI†‡, Guoqing XIA*1, Christian CLEMENT†‡, Deepak SHUKLA†‡ and Jian LIU*2
*Division of Medicinal Chemistry and Natural Products, School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, U.S.A., †Department of Ophthalmology and Visual Sciences, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, U.S.A., and ‡Department of Microbiology and Immunology, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, U.S.A.
Heparan sulphate (HS) 3-O-sulphotransferase transfers sulphate to the 3-OH position of the glucosamine residue of HS to form 3-O-sulphated HS. The HS modified by 3-O-sulphotransferase isoform 3 binds to HSV-1 (herpes simplex virus type 1) gD (envelope glycoprotein D), and the resultant 3-O-sulphated HS serves as an entry receptor for HSV-1. In the present paper, we report the isolation and characterization of a novel HS 3-O-sulphotransferase isoform, designated HS 3-O-sulphotransferase isoform 6 (3-OST-6). Mouse 3-OST-6 gene was identified in the EST (expressed sequence tag) database and cloned into pcDNA3.1/Myc-His vector. A CHO (Chinese-hamster ovary) cell line that stably expresses 3-OST-6 (3OST6/CHO cells) was prepared. The disaccharide analysis of the HS isolated from 3OST6/CHO cells revealed that 3-OST-6 exhibits HS 3-O-sulphotransferase activity. Furthermore, 3OST6/CHO cells were susceptible to infection by HSV-1, but not by other alphaherpesviruses examined, suggesting that 3-OST-6 produces a specific entry receptor for HSV-1. Our results indicate that a new member of 3-OST family generates an entry receptor for HSV-1. The findings add to the growing body of evidence that HSV-1 entry is mediated by 3-O-sulphated HS generated by multiple members of 3-O-sulphotransferases.
Key words: heparan sulphate, heparin, herpes simplex virus (HSV), sulphotransferase, viral entry.
Abbreviations used: AnMan3S, 2,5-anhydromannitol 3-O-sulphate; AnMan6S, 2,5-anhydromannitol 6-O-sulphate; AnMan3S6S, 2,5-anhydromannitol 3,6-O-disulphate; AT, antithrombin; BHV-1, bovine herpesvirus; CHO, Chinese-hamster ovary; Con A, concanavalin A; EST, expressed sequence tag; gB (etc.), envelope glycoprotein B (etc.); GlcA, glucuronic acid; HS, heparan sulphate; HSV-1, herpes simplex virus type 1; HVEM, herpesvirus entry mediator; IdoA, a-iduronic acid; IdoA2S, L-iduronic acid 2-O-sulphate; MTN, Multiple Tissue Northern; ORF, open reading frame; 3-OST, HS 3-O-sulphotransferase; PAPS, adenosine 3´-phosphate 5´-phosphosulphate; PRV, pseudorabies virus; RPIP-HPLC, reverse-phase ion-pairing HPLC.
1Present address: Division of Medical and Biochemical Microbiology, Research Centre Borstel, Parkallee 22, D-23845 Borstel, Germany.
2To whom correspondence should be addressed at Room 309, Beard Hall, University of North Carolina, Chapel Hill, NC 27599, U.S.A. (email jian_liu@unc.edu).
The nucleotide sequence reported in this paper has been submitted to the DDBJ, EMBL, GenBank® and GSDB Nucleotide Sequence Databases under accession number AY574375.
Received 28 May 2004/21 July 2004; accepted 10 August 2004
Published as BJ Immediate Publication 10 August 2004, DOI 10.1042/BJ20040908
The Biochemical Society, London ©2005
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