Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:4.2.2.7 (heparinase)
 1,270 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Membrane fusion induced by herpes simplex virus (HSV) is required for both entry and cell-to-cell spread. It is mediated by the viral glycoprotein gB, gD, gH-gL and gD receptors. Although 3-O-sulfated heparan sulfate (3-OS HS) is a receptor for HSV-1 entry, the requirement for heparan sulfate in the fusion process has been ruled out. Here, it is demonstrated that cells expressing 3-OS HS, generated by D-glucosaminyl 3-O-sulfotransferase isoforms-3 and/or -5 (3-OST-3 and 3-OST-5), fused with cells expressing the four glycoproteins. The cell fusion observed exhibited similar requirements but was independent of protein receptors, HVEM or nectin-1. Additionally, removal of 3-OS HS from the cell surface by heparinase-I treatment and, in separate experiments, the presence of soluble 3-OST-3- and 3-OST-5-modified HS, significantly inhibited fusion. Taken together, these results indicate that 3-OS HS can play a crucial role in virus entry and cell fusion.
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PMID:A role for 3-O-sulfated heparan sulfate in cell fusion induced by herpes simplex virus type 1. 1503 23

Cell surface heparan sulfate functions as a co-receptor in HSV-1 entry. In order to study its significance in context with specific gD receptors (nectin-1, HVEM, and 3-O-sulfated heparan sulfate) a low speed centrifugation based virus inoculation (spinoculation) method was used. The experiments were performed at 1200 x g using glycosylaminoglycan positive (GAG+) or deficient (GAG-) cells expressing gD receptors. Clearly, spinoculation of GAG- nectin-1 or HVEM cells enhanced significantly viral entry compared to similar but unspun cells. The enhanced entry was due to increased virus deposition at the cell surface and not due to pelleting of the virus. Among the gD receptors, spinoculated GAG- HVEM cells showed restoration of HSV-1 entry compared to unspinoculated GAG+ HVEM cells. In contrast, spinoculated GAG- nectin-1 cells showed less entry than unspinoculated GAG+ nectin-1 cells. GAG- 3-O-sulfotransferase-expressing cells or heparinase treated GAG+ 3-O-sulfated heparan sulfate cells, in contrast, remained resistant to entry even after spinoculation. To investigate further, any potential effects of centrifugation on membrane fusion, a virus-free cell fusion assay was performed. Clearly, spinning had no effects on cell fusion, nor could it replace the need for all four essential glycoproteins. Taken together these results suggest that heparan sulfate plays a role of an attachment receptor, which could be substituted by spinoculation. This effect, however, varies with the gD receptor used, which in turn, could be used as a means for identifying gD receptor usage for entry into a cell type.
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PMID:Spinoculation of heparan sulfate deficient cells enhances HSV-1 entry, but does not abolish the need for essential glycoproteins in viral fusion. 1590 19

Herpes simplex virus type 1 (HSV-1) infection of the corneal stroma remains a major cause of blindness. Primary cultures of corneal fibroblasts (CF) were tested and found susceptible to HSV-1 entry, which was confirmed by deconvolution imaging of infected cells. Plaque assay and real-time PCR demonstrated viral replication and hence a productive infection of CF by HSV-1. A role for glycoprotein D (gD) receptors in cultured CF was determined by gD interference assay. Reverse transcription-PCR analysis indicated expression of herpesvirus entry mediator and 3-O-sulfated (3-OS) heparan sulfate (HS)-generating enzyme 3-O sulfotransferase 3 (3-OST-3) but not nectin-1 or nectin-2. Subsequently, HS isolated from these cells was found to contain two distinct disaccharides (IdoUA2S-AnMan3S and IdoUA2S-AnMan3S6S) that are representative of 3-OST-3 activity. The following lines of evidence supported the important role of 3-OS HS as the mediator of HSV-1 entry into CF. (i) Blockage of entry was observed in CF treated with heparinases. The same enzymes had significantly less effect on HeLa cells that use nectin-1 as the entry receptor. (ii) Enzymatic removal of cell surface HS also removed the major gD-binding receptor, as evident from the reduced binding of gD to cells. (iii) Spinoculation assay demonstrated that entry blockage by heparinase treatment included the membrane fusion step. (iv) HSV-1 glycoprotein-induced cell-to-cell fusion was inhibited by either prior treatment of cells with heparinases or by HS preparations enriched in 3-OS HS. Taken together, the data in this report provide novel information on the role of 3-OS HS in mediating infection of CF, a natural target cell type.
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PMID:Role for 3-O-sulfated heparan sulfate as the receptor for herpes simplex virus type 1 entry into primary human corneal fibroblasts. 1694 May 9

Hematopoietic stem cells recipients remain susceptible to opportunistic viral infections including herpes simplex virus type-1 (HSV-1). The purpose of this investigation was to analyze susceptibility of human mesenchymal stem cells (hMSCs) to HSV-1 infection and identify the major entry receptor. Productive virus infection in hMSCs was confirmed by replication and plaque formation assays using a syncytial HSV-1 KOS (804) virus. To examine the significance of entry receptors, RT-PCR and antibody-blocking assays were performed. RT-PCR data showed the expression of gD receptors: nectin-1, 3-O sulfotransferase-3 (3-OST-3), and HVEM. Antibody-blocking assay together with heparinase treatment suggested an important role for HS and 3-O-sulfated heparan sulfate (3-OS HS), but not nectin-1 or HVEM, in mediating HSV-1 entry and spread in hMSCs. Taken together, our results provide strong evidence demonstrating that HSV-1 is capable of infecting hMSCs and HS and 3-OS HS serve as its entry receptors during this process.
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PMID:Herpes simplex virus type-1 (HSV-1) entry into human mesenchymal stem cells is heavily dependent on heparan sulfate. 2179 59