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Molecules 2015, 20(2), 2707-2727; doi:10.3390/molecules20022707

Diversity of Heparan Sulfate and HSV Entry: Basic Understanding and Treatment Strategies

1
Department of Microbiology & Immunology, Chicago College of Osteopathic Medicine, Midwestern University, Downers Grove, IL 60515, USA
2
Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL 60612, USA
3
Department of Microbiology & Immunology, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Vito Ferro
Received: 22 December 2014 / Accepted: 2 February 2015 / Published: 5 February 2015
(This article belongs to the Special Issue Glycosaminoglycans and Their Mimetics)
View Full-Text   |   Download PDF [797 KB, uploaded 10 February 2015]   |  

Abstract

A modified form of heparan sulfate (HS) known as 3-O-sulfated heparan sulfate (3-OS HS) generates fusion receptor for herpes simplex virus (HSV) entry and spread. Primary cultures of corneal fibroblasts derived from human eye donors have shown the clinical significance of this receptor during HSV corneal infection. 3-OS HS- is a product of a rare enzymatic modification at C3 position of glucosamine residue which is catalyzed by 3-O-sulfotransferases (3-OSTs) enzymes. From humans to zebrafish, the 3-OST enzymes are highly conserved and widely expressed in cells and tissues. There are multiple forms of 3-OSTs each producing unique subset of sulfated HS making it chemically diverse and heterogeneous. HSV infection of cells or zebrafish can be used as a unique tool to understand the structural-functional activities of HS and 3-OS HS and likewise, the infection can be used as a functional assay to screen phage display libraries for identifying HS and 3-OS HS binding peptides or small molecule inhibitors. Using this approach over 200 unique 12-mer HS and 3-OS HS recognizing peptides were isolated and characterized against HSV corneal infection where 3-OS HS is known to be a key receptor. In this review we discuss emerging role of 3-OS HS based therapeutic strategies in preventing viral infection and tissue damage. View Full-Text
Keywords: herpes simplex virus; 3-O sulfated heparan sulfate; 3-O sulfotransferase; viral entry herpes simplex virus; 3-O sulfated heparan sulfate; 3-O sulfotransferase; viral entry
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Tiwari, V.; Tarbutton, M.S.; Shukla, D. Diversity of Heparan Sulfate and HSV Entry: Basic Understanding and Treatment Strategies. Molecules 2015, 20, 2707-2727.

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