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Integrin alpha v beta 5 selectively promotes adenovirus mediated cell membrane permeabilization
T J Wickham1, E J Filardo, D A Cheresh
1Department of Immunology, Scripps Research Institute, La Jolla, California 92037.
The Journal of Cell Biology
|October 1, 1994
Summary
Human adenovirus type 2 uses integrin alpha v beta 5 for cell entry and membrane permeabilization, enhancing infection and gene delivery. This highlights a key role for integrin alpha v beta 5 in adenovirus infectious pathways.
Area of Science:
- Virology
- Cell Biology
- Molecular Medicine
Background:
- Human adenovirus type 2 (Ad2) utilizes receptor-mediated endocytosis for host cell entry.
- The virus penton base interacts with cell surface integrins, specifically alpha v beta 3 and alpha v beta 5, to initiate infection.
Purpose of the Study:
- To investigate the distinct roles of integrins alpha v beta 3 and alpha v beta 5 in Ad2 infection.
- To determine the involvement of these integrins in Ad2-induced membrane permeabilization and viral entry.
Main Methods:
- Transfection of cells with beta 5 or beta 3 subunits to express alpha v beta 5 and alpha v beta 3 integrins.
- Assessing Ad2 infection susceptibility and membrane permeabilization in cells expressing different integrins.
- Evaluating adenovirus-mediated gene delivery efficiency.
Main Results:
- Cells expressing alpha v beta 5 showed significantly higher susceptibility to Ad2-induced membrane permeabilization and infection compared to those with alpha v beta 3.
- Adenovirus-mediated gene delivery was more efficient in cells expressing alpha v beta 5.
- Integrin alpha v beta 5 plays a crucial role in facilitating Ad2 penetration post-internalization.
Conclusions:
- Integrin alpha v beta 5 is critical for Ad2-induced membrane permeabilization, a key step in the viral infectious pathway.
- The interaction between Ad2 penton base and alpha v beta 5 enhances virus penetration and infection efficiency.
- This study identifies a novel biological role for integrin alpha v beta 5 in adenovirus pathogenesis.