Characterization of heparan sulphate 3-O-sulphotransferase isoform 6 and its role in assisting the entry of herpes simplex virus type 1.
Characterization of heparan sulphate 3-O-sulphotransferase isoform 6 and its role in assisting the entry of herpes simplex virus type 1.
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DOI：
10.1042/bj20040908
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发表时间：
2005-01
期刊：
影响因子：
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通讯作者：
Ding Xu;V. Tiwari;Guoqing Xia;C. Clement;D. Shukla;Jian Liu
中科院分区：
文献类型：
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作者：
Ding Xu;V. Tiwari;Guoqing Xia;C. Clement;D. Shukla;Jian Liu
硫酸乙酰肝素 (HS) 3-O-磺基转移酶将硫酸盐转移至 HS 的葡萄糖胺残基的 3-OH 位置，形成 3-O-硫酸化 HS。经 3-O-磺基转移酶亚型 3 修饰的 HS 与 HSV-1（单纯疱疹病毒 1 型）gD（包膜糖蛋白 D）结合，所得的 3-O-硫酸化 HS 作为 HSV-1 的进入受体。在本文中，我们报告了一种新型 HS 3-O-磺基转移酶亚型的分离和表征，命名为 HS 3-O-磺基转移酶亚型 6 (3-OST-6)。小鼠3-OST-6基因在EST（表达序列标签）数据库中被鉴定并克隆到pcDNA3.1/Myc-His载体中。制备稳定表达3-OST-6的CHO（中国仓鼠卵巢）细胞系（3OST6/CHO细胞）。对从 3OST6/CHO 细胞中分离的 HS 的二糖分析表明，3-OST-6 表现出 HS 3-O-磺基转移酶活性。此外，3OST6/CHO 细胞易受 HSV-1 感染，但不易受其他检测的 α 疱疹病毒感染，这表明 3-OST-6 产生 HSV-1 的特异性进入受体。我们的结果表明 3-OST 家族的新成员产生 HSV-1 的进入受体。这些发现进一步证明 HSV-1 进入是由 3-O-磺基转移酶的多个成员产生的 3-O-硫酸化 HS 介导的。
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.