Coxsackie and Adenovirus Receptor Binding Ablation Reduces Adenovirus Liver Tropism and Toxicity

2005 ◽  
Vol 16 (2) ◽  
pp. 248-261 ◽  
Author(s):  
Chae-Ok Yun ◽  
A-Rum Yoon ◽  
Ji Young Yoo ◽  
Hoguen Kim ◽  
Minjung Kim ◽  
...  
2018 ◽  
Author(s):  
Alexander T. Baker ◽  
Alexander Greenshields-Watson ◽  
Lynda Coughlan ◽  
James A. Davies ◽  
Hanni Uusi-Kerttula ◽  
...  

ABSTRACTAdenovirus based vectors are of increasing importance for wide ranging therapeutic applications. As vaccines, vectors derived from human adenovirus species D serotypes 26 and 48 (HAdV-D26/48) are demonstrating promising efficacy as protective platforms against infectious diseases. Significant clinical progress has been made, yet definitive studies underpinning mechanisms of entry, infection, and receptor usage are currently lacking. Here, we performed structural and biological analysis of the receptor binding fiber-knob protein of HAdV-D26/48, reporting crystal structures, and modelling putative interactions with two previously suggested attachment receptors, CD46 and Coxsackie and Adenovirus Receptor (CAR). We provide evidence of a low affinity interaction with CAR, with modelling suggesting affinity is attenuated through extended, semi-flexible loop structures, providing steric hindrance. Conversely,in silicoandin vitroexperiments are unable to provide evidence of interaction between HAdV-D26/48 fiber-knob with CD46, or with Desmoglein 2. Our findings provide new insight to the cell-virus interactions of HAdV-D26/48, with important implications for the design and engineering of optimised Ad-based therapeutics.


2006 ◽  
Vol 13 ◽  
pp. S58-S59
Author(s):  
Minjung Kim ◽  
A-Rum Yoon ◽  
Ji Young Yoo ◽  
Min-Ju Kim ◽  
Yoon-A Kang ◽  
...  

2009 ◽  
Vol 28 (3) ◽  
pp. 268-274 ◽  
Author(s):  
Katrin Küster ◽  
Carsten Grötzinger ◽  
Annika Koschel ◽  
Andreas Fischer ◽  
Bertram Wiedenmann ◽  
...  

2005 ◽  
Vol 16 (6) ◽  
pp. 2694-2703 ◽  
Author(s):  
Ke Zen ◽  
Yuan Liu ◽  
Ingrid C. McCall ◽  
Tao Wu ◽  
Winston Lee ◽  
...  

Neutrophil (polymorphonuclear leukocytes [PMN]) transepithelial migration during inflammatory episodes involves a complex series of adhesive interactions and signaling events. Previous studies have shown that key adhesive interactions between leukocyte CD11b/CD18 and basally expressed fucosylated glycoproteins followed by binding to desmosomal-associated JAM-C are key elements of the transmigration response. Here we provide the first evidence that PMN-expressed junctional adhesion molecule-like protein (JAML) regulates transmigration via binding interactions with epithelial coxsackie and adenovirus receptor (CAR). Experiments with a JAML fusion protein revealed specific binding of JAML to epithelial CAR expressed at tight junctions in T84 cell monolayers and normal human colonic mucosa. Furthermore, JAML-CAR binding is mediated via the membrane distal immunoglobulin (Ig) loop of CAR and the membrane proximal Ig loop of JAML. PMN bound to immobilized CAR but not JAML in a divalent cation-independent manner. Lastly, in assays of PMN transepithelial migration, JAML/CAR fusion proteins and their antibodies significantly inhibited transmigration in a specific manner. Taken together, these results indicate that JAML and CAR are a novel pair of adhesion molecules that play an important role in modulating PMN migration cross epithelial tight junctions. These findings add a new element to a multistep model of PMN transepithelial migration and may provide new targets for anti-inflammatory therapies.


PLoS ONE ◽  
2010 ◽  
Vol 5 (3) ◽  
pp. e9909 ◽  
Author(s):  
Katherine J. D. A. Excoffon ◽  
Nicholas D. Gansemer ◽  
Matthew E. Mobily ◽  
Philip H. Karp ◽  
Kalpaj R. Parekh ◽  
...  

PLoS ONE ◽  
2012 ◽  
Vol 7 (5) ◽  
pp. e37523 ◽  
Author(s):  
Momina Mirza ◽  
Mei-Fong Pang ◽  
Mohamad Amr Zaini ◽  
Paula Haiko ◽  
Tuomas Tammela ◽  
...  

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