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Cryo-Em Imaging of a Pseudotyped Adenovhtus with Ocular Cell Tropism

Published online by Cambridge University Press:  02 July 2020

P.L. Stewart
Affiliation:
Crump Institute for Biological Imaging and Department of Molecular & Medical Pharmacology, UCLA School of Medicine, Los Angeles, CA90095
C.Y. Chiu
Affiliation:
Crump Institute for Biological Imaging and Department of Molecular & Medical Pharmacology, UCLA School of Medicine, Los Angeles, CA90095
D. Von Seggern
Affiliation:
Department of Immunology, The Scripps Research Institute, La Jolla, CA92037
G.R. Nemerow
Affiliation:
Department of Immunology, The Scripps Research Institute, La Jolla, CA92037
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Extract

Human adenovirus (Ad) provides unique model system for studying the multistage events in viral entry. We are applying cryo-electron microscopy and single particle reconstruction methods to study the cell entry pathway of Ad as well as to examine the structure of reengineered Ad vectors. Ad cell entry is mediated by interactions with two different cellular receptors: the fiber receptor, CAR for most Ad serotypes or a 50 kDa receptor for a subset of serotypes including Ad37, for attachment; and the αvβ3 and αvβ5 integrins for internalization. We have previously reconstructed both Ad2 and Adl2 virus particles complexed with a soluble form of αvβ5 integrin. We learned during our comparative cryo-EM study of the Ad2/αvβ5 and Adl2/αvβ5 complexes that the length of the variable RGD loop in the penton base affects the relative height of the integrin density over the penton base.

Type
Electron Cryomicroscopy of Macromolecules
Copyright
Copyright © Microscopy Society of America

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References

1Chiu, C Y. et al., “Structure of Adenovirus Complexed with its Internalization Receptor, αvβ5 Integrin.” J. Virology (1999) 73:6759.CrossRefGoogle Scholar
2.Von Seggern, D. J. et al., “A Helper Independent Adenoviral Vector Deleted for El, E3, and Fiber: Structure and Infectivity of Fiberless Particles.” J. Virology (1999) 73:1601.CrossRefGoogle Scholar
3.Bewley, M. C. et al., “Structural Analysis of the Mechanism of Adenovirus Binding to its Human Cellular Receptor, CAR.” Science (1999) 286:1579.CrossRefGoogle Scholar
4. This research was supported by N.I.H. grants AI42929 to P.L.S. and EY11431 to G.R.N.Google Scholar