scholarly journals Human Adenovirus 52 Uses Sialic Acid-containing Glycoproteins and the Coxsackie and Adenovirus Receptor for Binding to Target Cells

2015 ◽  
Vol 11 (2) ◽  
pp. e1004657 ◽  
Author(s):  
Annasara Lenman ◽  
A. Manuel Liaci ◽  
Yan Liu ◽  
Carin Årdahl ◽  
Anandi Rajan ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Human Adenovirus ◽  
Target Cells ◽  
Coxsackie And Adenovirus Receptor ◽  
Adenovirus Receptor

scholarly journals Polysialic acid is a cellular receptor for human adenovirus 52

2018 ◽  
Vol 115 (18) ◽  
pp. E4264-E4273 ◽  
Author(s):  
Annasara Lenman ◽  
A. Manuel Liaci ◽  
Yan Liu ◽  
Lars Frängsmyr ◽  
Martin Frank ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Electrostatic Interactions ◽  
Polysialic Acid ◽  
Human Adenovirus ◽  
Short Fiber ◽  
Dynamics Simulation ◽  
Target Cells ◽  
Cellular Receptor ◽  
Viral Pathogen ◽  
X Ray Crystallography

Human adenovirus 52 (HAdV-52) is one of only three known HAdVs equipped with both a long and a short fiber protein. While the long fiber binds to the coxsackie and adenovirus receptor, the function of the short fiber in the virus life cycle is poorly understood. Here, we show, by glycan microarray analysis and cellular studies, that the short fiber knob (SFK) of HAdV-52 recognizes long chains of α-2,8-linked polysialic acid (polySia), a large posttranslational modification of selected carrier proteins, and that HAdV-52 can use polySia as a receptor on target cells. X-ray crystallography, NMR, molecular dynamics simulation, and structure-guided mutagenesis of the SFK reveal that the nonreducing, terminal sialic acid of polySia engages the protein with direct contacts, and that specificity for polySia is achieved through subtle, transient electrostatic interactions with additional sialic acid residues. In this study, we present a previously unrecognized role for polySia as a cellular receptor for a human viral pathogen. Our detailed analysis of the determinants of specificity for this interaction has general implications for protein–carbohydrate interactions, particularly concerning highly charged glycan structures, and provides interesting dimensions on the biology and evolution of members ofHuman mastadenovirus G.

scholarly journals Diversity within the adenovirus fiber knob hypervariable loops influences primary receptor interactions

2018 ◽  
Author(s):  
Alexander T. Baker ◽  
Alexander Greenshields-Watson ◽  
Lynda Coughlan ◽  
James A. Davies ◽  
Hanni Uusi-Kerttula ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Steric Hindrance ◽  
Human Adenovirus ◽  
Coxsackie And Adenovirus Receptor ◽  
Flexible Loop ◽  
Receptor Interactions ◽  
Virus Interactions ◽  
Adenovirus Receptor ◽  
Affinity Interaction

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.

scholarly journals Initial Interactions of Subgenus D Adenoviruses with A549 Cellular Receptors: Sialic Acid versus αvIntegrins

2000 ◽  
Vol 74 (16) ◽  
pp. 7691-7693 ◽  
Author(s):  
Niklas Arnberg ◽  
Alistair H. Kidd ◽  
Karin Edlund ◽  
Farzad Olfat ◽  
Göran Wadell
Keyword(s):  
Sialic Acid ◽  
Adenovirus Type ◽  
Target Cells ◽  
Cellular Receptor ◽  
Cellular Receptors ◽  
Coxsackie Adenovirus Receptor ◽  
Acid Versus ◽  
Adenovirus Receptor

ABSTRACT Selected members of the adenovirus family have been shown to interact with the coxsackie adenovirus receptor, αvintegrins, and sialic acid on target cells. Initial interactions of subgenus D adenoviruses with target cells have until now been poorly characterized. Here, we demonstrate that adenovirus type 8 (Ad8), Ad19a, and Ad37 use sialic acid as a functional cellular receptor, whereas the Ad9 and Ad19 prototypes do not.

The endosomal epsilon-coatomer protein is involved in human adenovirus type 5 internalisation

2002 ◽  
Vol 50 (4) ◽  
pp. 481-489 ◽  
Author(s):  
Cs. Jeney ◽  
Boglárka Banizs ◽  
Orsolya Dobay ◽  
Keyword(s):  
Chinese Hamster ◽  
Human Adenovirus ◽  
Adenovirus Type ◽  
Inhibitory Effect ◽  
Bafilomycin A1 ◽  
Cho Cell ◽  
Coxsackie Adenovirus Receptor ◽  
Downstream Effector ◽  
Adenovirus Receptor ◽  
Adenovirus Type 5

The effects of bafilomycin A1 and of the reduced level of endosomal epsilon-COP (coatomer protein) on the infectivity of human adenovirus type 5 were investigated in Coxsackie adenovirus receptor- (CAR-) transfected Chinese hamster ovary (CHO) cells. The endosomal proton pump inhibitor bafilomycin A1 was able to cause only partial inhibition. Using ldlF cells (an epsilon-COP thermosensitive mutant CHO cell line) the reduction of epsilon-COP level also had partial inhibitory effect. Based on these results and comparing them to existing models of the adenovirus entry, we propose a refined model in which there are two pathways of adenoviral entry: the first one involves the epsilon-COP as the downstream effector of the acidification and can be blocked by bafilomycin A1 and the second one is a pH-independent pathway.

Sodium Butyrate Increases Expression of the Coxsackie and Adenovirus Receptor in Colon Cancer Cells

2009 ◽  
Vol 28 (3) ◽  
pp. 268-274 ◽  
Author(s):  
Katrin Küster ◽  
Carsten Grötzinger ◽  
Annika Koschel ◽  
Andreas Fischer ◽  
Bertram Wiedenmann ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Sodium Butyrate ◽  
Colon Cancer Cells ◽  
Coxsackie And Adenovirus Receptor ◽  
Adenovirus Receptor

scholarly journals Chimpanzee adenovirus CV-68 adapted as a gene delivery vector interacts with the coxsackievirus and adenovirus receptor

2002 ◽  
Vol 83 (1) ◽  
pp. 151-155 ◽  
Author(s):  
Christopher J. Cohen ◽  
Zhi Quan Xiang ◽  
Guang-Ping Gao ◽  
Hildegund C. J. Ertl ◽  
James M. Wilson ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Cho Cells ◽  
Human Adenovirus ◽  
Adenovirus Type ◽  
Soluble Form ◽  
Delivery Vector ◽  
Coxsackievirus And Adenovirus Receptor ◽  
Adenovirus Receptor ◽  
Adenovirus Type 5 ◽  
Dependent Mechanism

A replication-defective form of chimpanzee adenovirus type 68 (C68) has been developed to circumvent problems posed by widespread preexisting immunity to common human adenovirus vectors. To investigate the determinants of C68 tropism, its interaction with the coxsackievirus and adenovirus receptor (CAR) was studied. Although CHO cells were resistant to transduction by C68 as well as by adenovirus type 5 (Ad5), CHO cells expressing either human or murine CAR were transduced readily. C68 transduction, like Ad5 transduction, was blocked when cells were exposed to anti-CAR antibody or when virus was exposed to a soluble form of the CAR extracellular domain. These results indicate that gene delivery by C68 occurs by a CAR-dependent mechanism.

scholarly journals Neutrophil Migration across Tight Junctions Is Mediated by Adhesive Interactions between Epithelial Coxsackie and Adenovirus Receptor and a Junctional Adhesion Molecule-like Protein on Neutrophils

2005 ◽  
Vol 16 (6) ◽  
pp. 2694-2703 ◽  
Author(s):  
Ke Zen ◽  
Yuan Liu ◽  
Ingrid C. McCall ◽  
Tao Wu ◽  
Winston Lee ◽  
...  
Keyword(s):  
Tight Junctions ◽  
Adhesion Molecule ◽  
Specific Binding ◽  
Neutrophil Migration ◽  
Independent Manner ◽  
Coxsackie And Adenovirus Receptor ◽  
Cell Monolayers ◽  
Adhesive Interactions ◽  
Multistep Model ◽  
Adenovirus Receptor

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.

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