| Role for 3-O-sulfated heparan sulfate as the receptor for herpes simplex virus type 1 entry into primary human corneal fibroblasts. | |
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MedLine Citation:
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PMID: 16940509 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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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Authors:
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Vaibhav Tiwari; Christian Clement; Ding Xu; Tibor Valyi-Nagy; Beatrice Y J T Yue; Jian Liu; Deepak Shukla |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of virology Volume: 80 ISSN: 0022-538X ISO Abbreviation: J. Virol. Publication Date: 2006 Sep |
Date Detail:
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Created Date: 2006-08-30 Completed Date: 2006-10-20 Revised Date: 2010-09-16 |
Medline Journal Info:
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Nlm Unique ID: 0113724 Medline TA: J Virol Country: United States |
Other Details:
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Languages: eng Pagination: 8970-80 Citation Subset: IM |
Affiliation:
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University of Illinois at Chicago, Lions of Illinois Eye Research Institute, M/C 648, 1855 West Taylor Street, Chicago, IL 60612, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals CHO Cells Cornea / cytology, virology* Cricetinae Disaccharides / chemistry Fibroblasts / cytology, virology* Glycoproteins / metabolism Hela Cells Heparin Lyase / metabolism Heparitin Sulfate / chemistry* Herpesvirus 1, Human / metabolism* Humans Protein Binding |
| Grant Support | |
ID/Acronym/Agency:
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R01 AI 050050/AI/NIAID NIH HHS; R01 AI 057860/AI/NIAID NIH HHS; R01 EY 03890/EY/NEI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Disaccharides; 0/Glycoproteins; 9050-30-0/Heparitin Sulfate; EC 4.2.2.7/Heparin Lyase |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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