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Sulfated glycosaminoglycans as viral decoy receptors for human adenovirus type 37

Title: Sulfated glycosaminoglycans as viral decoy receptors for human adenovirus type 37
Authors: Chandra, N
Liu, Y
Liu, J-X
Fraengsmyr, L
Wu, N
Silva, LM
Lindstrom, M
Chai, W
Domellof, FP
Feizi, T
Arnberg, N
Item Type: Journal Article
Abstract: Glycans on plasma membranes and in secretions play important roles in infection by many viruses. Species D human adenovirus type 37 (HAdV-D37) is a major cause of epidemic keratoconjunctivitis (EKC) and infects target cells by interacting with sialic acid (SA)-containing glycans via the fiber knob domain of the viral fiber protein. HAdV-D37 also interacts with sulfated glycosaminoglycans (GAGs), but the outcome of this interaction remains unknown. Here, we investigated the molecular requirements of HAdV-D37 fiber knob:GAG interactions using a GAG microarray and demonstrated that fiber knob interacts with a broad range of sulfated GAGs. These interactions were corroborated in cell-based assays and by surface plasmon resonance analysis. Removal of heparan sulfate (HS) and sulfate groups from human corneal epithelial (HCE) cells by heparinase III and sodium chlorate treatments, respectively, reduced HAdV-D37 binding to cells. Remarkably, removal of HS by heparinase III enhanced the virus infection. Our results suggest that interaction of HAdV-D37 with sulfated GAGs in secretions and on plasma membranes prevents/delays the virus binding to SA-containing receptors and inhibits subsequent infection. We also found abundant HS in the basement membrane of the human corneal epithelium, which may act as a barrier to sub-epithelial infection. Collectively, our findings provide novel insights into the role of GAGs as viral decoy receptors and highlight the therapeutic potential of GAGs and/or GAG-mimetics in HAdV-D37 infection.
Issue Date: 12-Mar-2019
Date of Acceptance: 9-Mar-2019
URI: http://hdl.handle.net/10044/1/70339
DOI: https://dx.doi.org/10.3390/v11030247
ISSN: 1999-4915
Publisher: MDPI AG
Journal / Book Title: Viruses
Volume: 11
Issue: 3
Copyright Statement: © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Keywords: Science & Technology
Life Sciences & Biomedicine
Virology
adenovirus
glycosaminoglycan
cellular receptor
decoy receptor
tropism
epidemic keratoconjunctivitis
antiviral drugs
SIALIC-ACID
EPITHELIAL DEBRIDEMENT
TYROSINE SULFATION
BINDING
VIRUS
INFLUENZA
PROTEOGLYCANS
FIBER
PATHOGENESIS
TROPISM
adenovirus
antiviral drugs
cellular receptor
decoy receptor
epidemic keratoconjunctivitis
glycosaminoglycan
tropism
Science & Technology
Life Sciences & Biomedicine
Virology
adenovirus
glycosaminoglycan
cellular receptor
decoy receptor
tropism
epidemic keratoconjunctivitis
antiviral drugs
SIALIC-ACID
EPITHELIAL DEBRIDEMENT
TYROSINE SULFATION
BINDING
VIRUS
INFLUENZA
PROTEOGLYCANS
FIBER
PATHOGENESIS
TROPISM
Publication Status: Published
Article Number: 247
Appears in Collections:Department of Surgery and Cancer