Next Article in Journal
Improvement of High Affinity and Selectivity on Biosensors Using Genetically Engineered Phage by Binding Isotherm Screening
Next Article in Special Issue
The CARD9-Associated C-Type Lectin, Mincle, Recognizes La Crosse Virus (LACV) but Plays a Limited Role in Early Antiviral Responses against LACV
Previous Article in Journal
Interferon-Independent Upregulation of Interferon-Stimulated Genes during Human Cytomegalovirus Infection is Dependent on IRF3 Expression
Previous Article in Special Issue
Decoy Receptor Interactions as Novel Drug Targets against EKC-Causing Human Adenovirus
Open AccessArticle

Sulfated Glycosaminoglycans as Viral Decoy Receptors for Human Adenovirus Type 37

1
Section of Virology, Department of Clinical Microbiology, Umeå University, SE-90185 Umeå, Sweden
2
Glycosciences Laboratory, Faculty of Medicine, Imperial College of London, Hammersmith Campus, London W12 0NN, UK
3
Department of Integrative Medical Biology, Umeå University, SE-90185 Umeå, Sweden
4
Department of Clinical Science, Ophthalmology, Umeå University, SE-90185 Umeå, Sweden
*
Author to whom correspondence should be addressed.
Viruses 2019, 11(3), 247; https://doi.org/10.3390/v11030247
Received: 21 February 2019 / Revised: 7 March 2019 / Accepted: 9 March 2019 / Published: 12 March 2019
(This article belongs to the Special Issue The Glycobiology of Viral Infections)
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. View Full-Text
Keywords: adenovirus; glycosaminoglycan; cellular receptor; decoy receptor; tropism; epidemic keratoconjunctivitis; antiviral drugs adenovirus; glycosaminoglycan; cellular receptor; decoy receptor; tropism; epidemic keratoconjunctivitis; antiviral drugs
Show Figures

Figure 1

MDPI and ACS Style

Chandra, N.; Liu, Y.; Liu, J.-X.; Frängsmyr, L.; Wu, N.; Silva, L.M.; Lindström, M.; Chai, W.; Pedrosa Domellöf, F.; Feizi, T.; Arnberg, N. Sulfated Glycosaminoglycans as Viral Decoy Receptors for Human Adenovirus Type 37. Viruses 2019, 11, 247.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop