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An Efficient Method for Adenovirus Production
Published on: June 10, 2021
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Diversity within the adenovirus fiber knob hypervariable loops influences primary receptor interactions
Alexander T Baker1, Alexander Greenshields-Watson2, Lynda Coughlan3
1Division of Cancer and Genetics, School of Medicine, Cardiff University, Cardiff, CF14 4XN, UK.
Nature Communications
|February 16, 2019
Summary
Adenovirus vectors HAdV-D26/48 show promise for vaccines. Research reveals low affinity for CAR and no interaction with CD46 or Desmoglein 2, guiding future therapeutic design.
Area of Science:
- Virology
- Structural Biology
- Immunology
Background:
- Adenovirus-based vectors are crucial for therapeutic applications, including vaccines.
- Human adenovirus species D serotypes 26 and 48 (HAdV-D26/48) show efficacy as vaccine platforms.
- Mechanisms of entry, infection, and receptor usage for HAdV-D26/48 remain incompletely understood.
Purpose of the Study:
- To structurally and biologically analyze the HAdV-D26/48 fiber-knob protein.
- To investigate interactions with potential attachment receptors: CD46, Coxsackie and Adenovirus Receptor (CAR), and Desmoglein 2.
Main Methods:
- Crystal structure determination of the HAdV-D26/48 fiber-knob protein.
- Computational modeling of protein-receptor interactions.
- In silico and in vitro binding assays.
Main Results:
- Crystal structures revealed details of the HAdV-D26/48 fiber-knob.
- Low-affinity interaction with CAR was observed, potentially hindered by flexible loops.
- No evidence of interaction with CD46 or Desmoglein 2 was found.
Conclusions:
- HAdV-D26/48 exhibits a low-affinity interaction with CAR, suggesting steric hindrance.
- The virus does not appear to interact with CD46 or Desmoglein 2.
- Findings inform the design of improved adenovirus-based therapeutics.
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