@article{Chandra:2019:10.3390/v11030247,
author = {Chandra, N and Liu, Y and Liu, J-X and Fraengsmyr, L and Wu, N and Silva, LM and Lindstrom, M and Chai, W and Domellof, FP and Feizi, T and Arnberg, N},
doi = {10.3390/v11030247},
journal = {Viruses},
title = {Sulfated glycosaminoglycans as viral decoy receptors for human adenovirus type 37},
url = {http://dx.doi.org/10.3390/v11030247},
volume = {11},
year = {2019}
}

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TY  - JOUR
AB  - 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.
AU  - Chandra,N
AU  - Liu,Y
AU  - Liu,J-X
AU  - Fraengsmyr,L
AU  - Wu,N
AU  - Silva,LM
AU  - Lindstrom,M
AU  - Chai,W
AU  - Domellof,FP
AU  - Feizi,T
AU  - Arnberg,N
DO  - 10.3390/v11030247
PY  - 2019///
SN  - 1999-4915
TI  - Sulfated glycosaminoglycans as viral decoy receptors for human adenovirus type 37
T2  - Viruses
UR  - http://dx.doi.org/10.3390/v11030247
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000464389700003&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - http://hdl.handle.net/10044/1/70339
VL  - 11
ER  - 

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