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A role for heparan sulfate 3-O-sulfotransferase isoform 2 in herpes simplex virus type 1 entry and spread.

机译:硫酸乙酰肝素3-O-磺基转移酶同工型2在单纯疱疹病毒1型进入和扩散中的作用。

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摘要

Heparan sulfate (HS) 3-O-sulfotransferase isoform-2 (3-OST-2), which belongs to a family of enzymes capable of generating herpes simplex virus type-1 (HSV-1) entry and spread receptors, is predominantly expressed in human brain. Despite its unique expression pattern, the ability of 3-OST-2 to mediate HSV-1 entry and cell-to-cell fusion is not known. Our results demonstrate that expression of 3-OST-2 can render Chinese hamster ovary K1 (CHO-K1) cells susceptible to entry of wild-type and mutant strains of HSV-1. Evidence for generation of gD receptors by 3-OST-2 were suggested by gD-mediated interference assay and the ability of 3-OST-2-expressing CHO-K1 cells to preferentially bind HSV-1 gD, which could be reversed by prior treatment of cells with HS lyases (heparinases II/III). In addition, 3-OST-2-expressing CHO-K1 cells acquired the ability to fuse with cells-expressing HSV-1 glycoproteins, a phenomenon that mimics a way of viral spread in vivo. Demonstrating specificity, the cell fusion was inhibited by soluble 3-O-sulfated forms of HS, but not unmodified HS. Taken together, our results raise the possibility of a role of 3-OST-2 in the spread of HSV-1 infection in the brain.
机译:主要表达硫酸乙酰肝素(HS)3-O-磺基转移酶同工型2(3-OST-2),该酶属于能够产生1型单纯疱疹病毒(HSV-1)进入和扩散受体的酶家族。在人脑中。尽管其独特的表达方式,但尚不知道3-OST-2介导HSV-1进入和细胞间融合的能力。我们的研究结果表明3-OST-2的表达可使中国仓鼠卵巢K1(CHO-K1)细胞易于进入野生型和突变株HSV-1。 gD介导的干扰测定法和3-OST-2表达的CHO-K1细胞优先结合HSV-1 gD的能力提出了3-OST-2产生gD受体的证据,这可以通过先前的治疗逆转HS裂解酶(肝素酶II / III)的细胞数量。此外,表达3-OST-2的CHO-K1细胞具有与表达HSV-1糖蛋白的细胞融合的能力,这种现象模仿了体内病毒传播的方式。证明特异性,细胞融合被可溶性3-O-硫酸化形式的HS抑制,但未被未修饰的HS抑制。综上所述,我们的结果提高了3-OST-2在HSV-1感染在脑中传播中的作用的可能性。

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