CD46 is a cellular receptor for group B adenoviruses

Area of Science:

• Virology
• Immunology
• Gene Therapy

Background:

• Group B adenoviruses cause severe illnesses in immunocompromised individuals.
• They are being explored as gene therapy vectors for refractory cell types.

Purpose of the Study:

• Identify the cellular attachment receptor for group B adenoviruses.
• Investigate the role of this receptor in viral infection and gene therapy.

Main Methods:

• Mass spectrometric analysis of group B adenovirus fiber protein interactions.
• Ectopic expression of potential receptors in nonhuman cells.
• siRNA-mediated knockdown and soluble receptor blocking assays.

Main Results:

• Human CD46 was identified as the cellular attachment receptor for group B adenoviruses.
• CD46 expression enabled infection of nonhuman cells in vitro and in vivo.
• CD46 knockdown or blocking inhibited group B adenovirus infection.

Conclusions:

• Group B adenoviruses utilize CD46, a complement regulatory protein, for cellular attachment.
• This finding explains disease manifestations and informs gene therapy vector design.