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Adenovirus type 11 uses CD46 as a cellular receptor
Anna Segerman1, John P Atkinson, Marko Marttila
1Department of Virology, Umeå University, SE-90185 Umeå, Sweden.
Journal of Virology
|August 14, 2003
Summary
Species B adenoviruses, like adenovirus type 11 (Ad11), do not use the common coxsackie-adenovirus receptor (CAR). This study identifies CD46 (membrane cofactor protein) as the cellular receptor for Ad11, enabling infection.
Area of Science:
- Virology
- Cell Biology
- Immunology
Background:
- Human adenoviruses comprise 51 serotypes across six species (A-F).
- Many adenoviruses utilize the coxsackie-adenovirus receptor (CAR) for host cell attachment.
- Species B adenoviruses, implicated in respiratory, ocular, and urinary tract diseases, do not compete with CAR-binding serotypes, suggesting an alternative receptor.
Purpose of the Study:
- To identify the cellular receptor used by species B adenoviruses, specifically adenovirus type 11 (Ad11).
- To investigate the role of CD46 (membrane cofactor protein) as a potential receptor for Ad11.
Main Methods:
- Transfection of Chinese hamster ovary (CHO) cells with cDNAs encoding CD46, CAR, or CD55 (decay accelerating factor).
- Binding assays using Ad11 virions and soluble fiber knob proteins from Ad11, Ad7, and Ad5.
- Infection assays with Ad11 on modified CHO cells and inhibition studies using anti-CD46 antibodies.
Main Results:
- Adenovirus type 11 (Ad11) exhibited significantly stronger binding (over 10-fold) to CHO cells expressing CD46 compared to those expressing CAR or CD55.
- Transfection of CD46-cDNA rendered nonpermissive CHO cells susceptible to Ad11 infection.
- Soluble Ad11 fiber knob inhibited Ad11 virion binding to CD46-transfected cells, and anti-CD46 antibodies blocked both Ad11 binding and infection.
Conclusions:
- CD46 serves as the cellular receptor for adenovirus type 11 (Ad11).
- This finding clarifies the host cell entry mechanism for species B adenoviruses.