PUBLICATION

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

Authors
Tiwari, V., Tarbutton, M.S., Shukla, D.
ID
ZDB-PUB-150211-18
Date
2015
Source
Molecules   20: 2707-2727 (Review)
Registered Authors
Tiwari, Vaibhav
Keywords
none
MeSH Terms
  • Animals
  • Carbohydrate Conformation
  • Heparitin Sulfate*/chemistry
  • Heparitin Sulfate*/metabolism
  • Humans
  • Keratitis, Herpetic*/drug therapy
  • Keratitis, Herpetic*/metabolism
  • Keratitis, Herpetic*/pathology
  • Simplexvirus/physiology*
  • Structure-Activity Relationship
  • Virus Internalization*
  • Zebrafish
PubMed
25665065 Full text @ Molecules
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.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping