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 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 Adenovirus Type 11 Uses CD46 as a Cellular Receptor

2003 ◽  
Vol 77 (17) ◽  
pp. 9183-9191 ◽  
Author(s):  
Anna Segerman ◽  
John P. Atkinson ◽  
Marko Marttila ◽  
Veronica Dennerquist ◽  
Göran Wadell ◽  
...  
Keyword(s):  
Cho Cells ◽  
Chinese Hamster ◽  
Human Adenovirus ◽  
Adenovirus Type ◽  
Host Cells ◽  
Cellular Receptor ◽  
Transfected Cells ◽  
Coxsackie Adenovirus Receptor ◽  
Adenovirus Receptor

ABSTRACT The 51 human adenovirus serotypes are divided into six species (A to F). Many adenoviruses use the coxsackie-adenovirus receptor (CAR) for attachment to host cells in vitro. Species B adenoviruses do not compete with CAR-binding serotypes for binding to host cells, and it has been suggested that species B adenoviruses use a receptor other than CAR. Species B adenoviruses mainly cause disease in the respiratory tract, the eyes, and in the urinary tract. Here we demonstrate that adenovirus type 11 (Ad11; of species B) binds to Chinese hamster ovary (CHO) cells transfected with CD46 (membrane cofactor protein)-cDNA at least 10 times more strongly than to CHO cells transfected with cDNAs encoding CAR or CD55 (decay accelerating factor). Nonpermissive CHO cells were rendered permissive to Ad11 infection upon transfection with CD46-cDNA. Soluble Ad11 fiber knob but not Ad7 or Ad5 knob inhibited binding of Ad11 virions to CD46-transfected cells, and anti-CD46 antibodies inhibited both binding of and infection by Ad11. From these results we conclude that CD46 is a cellular receptor for Ad11.

scholarly journals Conserved Surface Residues on the Feline Calicivirus Capsid Are Essential for Interaction with Its Receptor Feline Junctional Adhesion Molecule A (fJAM-A)

2018 ◽  
Vol 92 (8) ◽  
Author(s):  
Zhengchun Lu ◽  
Emily D. Ledgerwood ◽  
Meleana M. Hinchman ◽  
Robert Dick ◽  
John S. L. Parker
Keyword(s):  
Capsid Protein ◽  
Receptor Binding ◽  
Adhesion Molecule ◽  
Conformational Changes ◽  
Growth Kinetics ◽  
Feline Calicivirus ◽  
Viral Capsid ◽  
Virus Receptor ◽  
Receptor Interactions

ABSTRACTHost cell surface receptors are required for attachment, binding, entry, and infection by nonenveloped viruses. Receptor binding can induce conformational changes in the viral capsid and/or the receptor that couple binding with downstream events in the virus life cycle (intracellular signaling, endocytosis and trafficking, and membrane penetration). Virus-receptor interactions also influence viral spread and pathogenicity. The interaction between feline calicivirus (FCV) and its receptor, feline junctional adhesion molecule A (fJAM-A), on host cells is required for infection and induces irreversible, inactivating conformational changes in the capsid of some viral strains. Cryoelectron microscopy (cryo-EM) structures of FCV bound to fJAM-A showed several possible virus-receptor interactions. However, the specific residues on the viral capsid required for binding are not known. Capsid residues that may be involved in postbinding events have been implicated by isolation of soluble receptor-resistant (srr) mutants in which changes in the capsid protein sequence change the capacity of such srr mutants to be inactivated upon incubation with soluble fJAM-A. To clarify which residues on the surface of FCV are required for its interaction with fJAM-A and to potentially identify residues required for postreceptor binding events, we used the existing atomic-resolution structures of FCV and the FCV-fJAM-A cryo-EM structures to select 14 capsid residues for mutation and preparation of recombinant viral capsids. Using this approach, we identified residues on the FCV capsid that are required for fJAM-A binding and other residues that are not required for binding but are required for infection that are likely important for subsequent postbinding events.IMPORTANCEFeline calicivirus (FCV) is a common cause of mild upper respiratory disease in cats. Some FCV isolates can cause virulent systemic disease. The genetic determinants of virulence for FCV are unknown. We previously found that virulent FCV isolates have fasterin vitrogrowth kinetics than less virulent isolates. Differences in viral growthin vitromay correlate with differences in virulence. Here, we investigated the roles of specific FCV capsid residues on the receptor-virus interaction and viral growthin vitro. We show that the capsid protein genes of the virulent FCV-5 isolate determine its fasterin vitrogrowth kinetics compared to those of the nonvirulent FCV-Urbana infectious clone. We also identified residues on the capsid VP1 protein that are important for receptor binding or for steps subsequent to receptor binding. Our data provide further insight into the specific molecular interactions between fJAM-A and the FCV capsid that regulate binding and infectious entry.

scholarly journals 149. Coxsackie and Adenovirus Receptor Binding Ablation Reduces Adenovirus Liver Tropism and Toxicity

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

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 ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Coxsackie And Adenovirus Receptor ◽  
Adenovirus Receptor
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