scholarly journals A Zebrafish Coxsackievirus and Adenovirus Receptor Homologue Interacts with Coxsackie B Virus and Adenovirus

2002 ◽  
Vol 76 (20) ◽  
pp. 10503-10506 ◽  
Author(s):  
JenniElizabeth Petrella ◽  
Christopher J. Cohen ◽  
Jedidiah Gaetz ◽  
Jeffrey M. Bergelson
Keyword(s):  
Adenovirus Type ◽  
Extracellular Domain ◽  
Receptor Interaction ◽  
Transfected Cells ◽  
B Virus ◽  
Coxsackie B Virus ◽  
Coxsackievirus And Adenovirus Receptor ◽  
Adenovirus Receptor ◽  
Adenovirus Type 5 ◽  
Coxsackie B

ABSTRACT In this study, a zebrafish homologue of the coxsackievirus and adenovirus receptor (CAR) protein was identified. Although the extracellular domain of zebrafish CAR (zCAR) is less than 50% identical to that of human CAR (hCAR), zCAR mediated infection of transfected cells by both adenovirus type 5 and coxsackievirus B3. CAR residues interacting deep within the coxsackievirus canyon are highly conserved in zCAR and hCAR, which is consistent with the idea that receptor contacts within the canyon are responsible for coxsackievirus attachment. In contrast, CAR residues contacting the south edge of the canyon are not conserved, suggesting that receptor interaction with the viral “puff region” is not essential for attachment.

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 The Coxsackie B Virus and Adenovirus Receptor Resides in a Distinct Membrane Microdomain

2003 ◽  
Vol 77 (4) ◽  
pp. 2559-2567 ◽  
Author(s):  
Katherine J. D. Ashbourne Excoffon ◽  
Thomas Moninger ◽  
Joseph Zabner
Keyword(s):  
Lipid Raft ◽  
Density Lipoprotein ◽  
Cellular Adhesion ◽  
Immunoglobulin Superfamily ◽  
Viral Receptor ◽  
Membrane Microdomain ◽  
B Virus ◽  
Coxsackie B Virus ◽  
Adenovirus Receptor ◽  
Coxsackie B

ABSTRACT The coxsackie B virus and adenovirus receptor (CAR) is a member of the immunoglobulin superfamily. In addition to activity as a viral receptor, it may play a role in cellular adhesion. We asked what determines the cell membrane microdomain of CAR. We found that CAR is localized to a novel lipid-rich microdomain similar to that of the low-density lipoprotein receptor (LDLR) but distinct from that of a CAR variant that exhibited traditional lipid raft localization via fusion to a glycosylphosphatidylinositol (GPI) tail. The cytoplasmic tail determines its membrane localization, since deletion of this domain resulted in mislocalization. Results indicate that CAR, CAR-LDLR, and LDLR reside in a novel lipid raft that is distinct from caveolin-1-containing caveolae and GPI-linked proteins. Residence in a lipid-rich domain provides a mechanism that allows CAR to interact with other cell adhesion proteins and yet function as an adenovirus receptor.

Soluble coxsackie- and adenovirus receptor (sCAR-Fc); a highly efficient compound against laboratory and clinical strains of coxsackie-B-virus

2016 ◽  
Vol 136 ◽  
pp. 1-8 ◽  
Author(s):  
Sandra Pinkert ◽  
Babette Dieringer ◽  
Sabine Diedrich ◽  
Heinz Zeichhardt ◽  
Jens Kurreck ◽  
...  
Keyword(s):  
Coxsackie And Adenovirus Receptor ◽  
Clinical Strains ◽  
Highly Efficient ◽  
B Virus ◽  
Coxsackie B Virus ◽  
Adenovirus Receptor ◽  
Coxsackie B

scholarly journals The Human HLA-A*0201 Allele, Expressed in Hamster Cells, Is Not a High-Affinity Receptor for Adenovirus Type 5 Fiber

1999 ◽  
Vol 73 (5) ◽  
pp. 4513-4517 ◽  
Author(s):  
E. Davison ◽  
I. Kirby ◽  
T. Elliott ◽  
G. Santis
Keyword(s):  
Mhc Class I ◽  
Adenovirus Type ◽  
Class I ◽  
High Affinity ◽  
Histocompatibility Complex ◽  
B Virus ◽  
High Affinity Receptor ◽  
Affinity Receptor ◽  
Adenovirus Receptor ◽  
Adenovirus Type 5

ABSTRACT The coxsackie B virus and adenovirus receptor (CAR) and the major histocompatibility complex (MHC) class I α2 domain have been identified as high-affinity cell receptors for adenovirus type 5 (Ad5) fiber. In this study we show that CAR but not MHC class I allele HLA-A*0201 binds to Ad5 with high affinity when expressed on hamster cells. When both receptors are coexpressed on the cell surface of hamster cells, Ad5 fiber bind to a single high-affinity receptor, which is CAR.

scholarly journals Replication-Defective Vector Based on a Chimpanzee Adenovirus

2001 ◽  
Vol 75 (23) ◽  
pp. 11603-11613 ◽  
Author(s):  
Steven F. Farina ◽  
Guang-ping Gao ◽  
Z. Q. Xiang ◽  
John J. Rux ◽  
Roger M. Burnett ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Human Adenovirus ◽  
Adenovirus Type ◽  
Open Reading Frames ◽  
Hypervariable Regions ◽  
293 Cells ◽  
Coxsackievirus And Adenovirus Receptor ◽  
Cross Neutralization ◽  
Adenovirus Receptor ◽  
Adenovirus Type 5

ABSTRACT An adenovirus previously isolated from a mesenteric lymph node from a chimpanzee was fully sequenced and found to be similar in overall structure to human adenoviruses. The genome of this virus, called C68, is 36,521 bp in length and is most similar to subgroup E of human adenovirus, with 90% identity in most adenovirus type 4 open reading frames that have been sequenced. Substantial differences in the hexon hypervariable regions were noted between C68 and other known adenoviruses, including adenovirus type 4. Neutralizing antibodies to C68 were highly prevalent in sera from a population of chimpanzees, while sera from humans and rhesus monkeys failed to neutralize C68. Furthermore, infection with C68 was not neutralized from sera of mice immunized with human adenovirus serotypes 2, 4, 5, 7, and 12. A replication-defective version of C68 was created by replacing the E1a and E1b genes with a minigene cassette; this vector was efficiently transcomplemented by the E1 region of human adenovirus type 5. C68 vector transduced a number of human and murine cell lines. This nonhuman adenoviral vector is sufficiently similar to human serotypes to allow growth in 293 cells and transduction of cells expressing the coxsackievirus and adenovirus receptor. As it is dissimilar in regions such as the hexon hypervariable domains, C68 vector avoids significant cross-neutralization by sera directed against human serotypes.

scholarly journals Role of the putative heparan sulfate glycosaminoglycan-binding site of the adenovirus type 5 fiber shaft on liver detargeting and knob-mediated retargeting

2006 ◽  
Vol 87 (9) ◽  
pp. 2487-2495 ◽  
Author(s):  
Neus Bayo-Puxan ◽  
Manel Cascallo ◽  
Alena Gros ◽  
Meritxell Huch ◽  
Cristina Fillat ◽  
...  
Keyword(s):  
Heparan Sulfate ◽  
Adenovirus Type ◽  
Adenoviral Vectors ◽  
Coxsackievirus And Adenovirus Receptor ◽  
Protein Ix ◽  
Adenovirus Receptor ◽  
Adenovirus Type 5

Liver tropism hampers systemic administration of adenovirus in gene therapy and virotherapy. In consequence, tumour targeting requires the combination of capsid modifications that abrogate liver transduction and redirect adenoviral vectors to tumour cells. Coxsackievirus and adenovirus receptor (CAR), integrins and heparan sulfate glycosaminoglycans (HSG) are receptors involved in adenovirus type 5 (Ad5) entry into cells. The in vitro and in vivo properties of Ad5 vectors unable to bind CAR, integrins and HSG with and without Arg–Gly–Asp (RGD) inserted at the HI loop of the fiber were studied. As was previously observed with CAR-ablated vectors, CAR and integrin double binding-ablated vectors transduced hepatocytes less efficiently in vitro but not in vivo. On the contrary, the role of HSG on Ad5 infectivity was evident in vitro only when CAR binding was abrogated, but the shaft mutation that ablated HSG binding on the background of a normal capsid was sufficient to abrogate liver transduction in vivo. The insertion of amino acids RGD at the HI loop in a shaft-mutated fiber only partially rescued integrin-mediated infectivity. These results indicate that the shaft mutation precluded HSG binding and affected the structure of the fiber. The insertion of ligands at the hexon or protein IX may be required to benefit from the fiber shaft mutation-detargeting properties.

scholarly journals Adenovirus Type 9 Fiber Knob Binds to the Coxsackie B Virus-Adenovirus Receptor (CAR) with Lower Affinity than Fiber Knobs of Other CAR-Binding Adenovirus Serotypes

2001 ◽  
Vol 75 (15) ◽  
pp. 7210-7214 ◽  
Author(s):  
Ian Kirby ◽  
Rosemary Lord ◽  
Elizabeth Davison ◽  
Thomas J. Wickham ◽  
Peter W. Roelvink ◽  
...  
Keyword(s):  
Adenovirus Type ◽  
Dissociation Rate ◽  
Site Directed Mutagenesis ◽  
Binding Modes ◽  
Binding Interaction ◽  
B Virus ◽  
Coxsackie B Virus ◽  
Contact Residues ◽  
Dissociation Rate Constants ◽  
Coxsackie B

ABSTRACT The coxsackie B virus and adenovirus (Ad) receptor (CAR) functions as an attachment receptor for multiple Ad serotypes. Here we show that the Ad serotype 9 (Ad9) fiber knob binds to CAR with much reduced affinity compared to the binding by Ad5 and Ad12 fiber knobs as well as the knob of the long fiber of Ad41 (Ad41L). Substitution of Asp222 in Ad9 fiber knob with a lysine that is conserved in Ad5, Ad12, and Ad41L substantially improved Ad9 fiber knob binding to CAR, while the corresponding substitution in Ad5 (Lys442Asp) significantly reduced Ad5 binding. The presence of an aspartic acid residue in Ad9 therefore accounts, at least in part, for the reduced CAR binding affinity of the Ad9 fiber knob. Site-directed mutagenesis of CAR revealed that CAR residues Leu73 and Lys121 and/or Lys123 are critical contact residues, with Tyr80 and Tyr83 being peripherally involved in the binding interaction with the Ad5, Ad9, Ad12, and Ad41L fiber knobs. The overall affinities and the association and dissociation rate constants for wild-type CAR as well as Tyr80 and Tyr83 CAR mutants differed between the serotypes, indicating that their binding modes, although similar, are not identical.

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