Characterization of heparan sulphate 3-O-sulphotransferase isoform 6 and its role in assisting the entry of herpes simplex virus type 1.
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.
Division of Medicinal Chemistry and Natural Products, School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, USA.
Ding
D
Xu
Vaibhav
V
Tiwari
Guoqing
G
Xia
Christian
C
Clement
Deepak
D
Shukla
Jian
J
Liu
D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D000991:Antithrombins / Q000378:metabolism; D001483:Base Sequence / Q000235:genetics; D016466:CHO Cells / Q000737:chemistry / Q000201:enzymology / Q000378:metabolism / Q000821:virology; D002459:Cell Fusion; D006224:Cricetinae; D003412:Cricetulus; D018076:DNA, Complementary / Q000235:genetics; D030541:Databases, Genetic; D006497:Heparan Sulfate / Q000378:metabolism; D006561:Herpes Simplex / Q000201:enzymology*; D018259:Herpesvirus 1, Human / Q000472:pathogenicity*; D006801:Humans; D008969:Molecular Sequence Data; D013379:Substrate Specificity / Q000235:genetics / Q000502:physiology; D015238:Sulfotransferases / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D014018:Tissue Distribution
D000991:Antithrombins; D018076:DNA, Complementary; D006497:Heparan Sulfate; D015238:Sulfotransferases; C501522:Hs3st6 protein, mouse; C021350:heparitin sulfotransferase