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Published on: August 13, 2013
CD46 is a cellular receptor for all species B adenoviruses except types 3 and 7
Marko Marttila1, David Persson, Dan Gustafsson
1Department of Virology, Umeå University, SE-901 85 Umeå, Sweden.
Abstract:
The 51 human adenovirus serotypes are divided into six species (A to F). Adenovirus serotypes from all species except species B utilize the coxsackie-adenovirus receptor for attachment to host cells in vitro. Species B adenoviruses primarily cause ocular and respiratory tract infections, but certain serotypes are also associated with renal disease. We have previously demonstrated that adenovirus type 11 (species B) uses CD46 (membrane cofactor protein) as a cellular receptor instead of the coxsackie-adenovirus receptor (A. Segerman et al., J. Virol. 77:9183-9191, 2003). In the present study, we found that transfection with human CD46 cDNA rendered poorly permissive Chinese hamster ovary cells more permissive to infection by all species B adenovirus serotypes except adenovirus types 3 and 7. Moreover, rabbit antiserum against human CD46 blocked or efficiently inhibited all species B serotypes except adenovirus types 3 and 7 from infecting human A549 cells. We also sequenced the gene encoding the fiber protein of adenovirus type 50 (species B) and compared it with the corresponding amino acid sequences from selected serotypes, including all other serotypes of species B. From the results obtained, we conclude that CD46 is a major cellular receptor on A549 cells for all species B adenoviruses except types 3 and 7.
Insights
Species B adenoviruses use CD46 as a cellular receptor for host cell entry, except for types 3 and 7. This finding is crucial for understanding adenovirus tropism and developing targeted therapies.
Area of Science:
- Virology
- Cell Biology
- Immunology
Background:
- Human adenoviruses are classified into six species (A-F).
- Most adenoviruses use the coxsackie-adenovirus receptor (CAR) for cell attachment.
- Species B adenoviruses are linked to ocular, respiratory, and renal diseases.
Purpose of the Study:
- To investigate the cellular receptor used by species B adenoviruses.
- To determine if CD46 serves as a receptor for species B adenoviruses.
- To identify the role of CD46 in adenovirus tropism.
Main Methods:
- Transfection of Chinese hamster ovary (CHO) cells with human CD46 cDNA.
- Infection assays using various species B adenovirus serotypes.
- Neutralization assays with rabbit antiserum against human CD46.
- Sequencing of the fiber protein gene of adenovirus type 50.
Main Results:
- CD46 expression increased CHO cell permissiveness to most species B adenoviruses, excluding types 3 and 7.
- Anti-CD46 antiserum inhibited infection by most species B adenoviruses in A549 cells, except for types 3 and 7.
- Fiber protein analysis provided insights into receptor-binding variations.
Conclusions:
- CD46 is a major cellular receptor for most species B adenoviruses on A549 cells.
- Adenovirus types 3 and 7 likely utilize a different cellular receptor.
- Understanding adenovirus-receptor interactions is key for disease control.
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