Alpha-defensin binding expands human adenovirus tropism

Area of Science:

• Immunology
• Virology
• Molecular Biology

Background:

• Mammalian α-defensins are key innate immune peptides with complex roles beyond direct antimicrobial activity.
• Some viruses, including human adenoviruses (HAdVs), can be enhanced by α-defensins, suggesting non-canonical interactions.
• Previous work indicated α-defensins can overcome inhibitors of HAdV cell binding, hinting at a defensin-mediated mechanism.

Purpose of the Study:

• To investigate a potential α-defensin-mediated binding mechanism for HAdVs that bypasses known viral receptors.
• To determine if this novel binding pathway is independent of primary viral receptors and co-receptors.
• To understand how α-defensins influence HAdV tropism and infection in the presence of altered receptor expression.

Main Methods:

• Genetic modification of host cells and HAdVs to block normal receptor-mediated infection pathways.
• Exposure of modified HAdVs to α-defensins in receptor-deficient or naturally non-susceptible cell systems.
• Assessment of cell binding and subsequent infection, focusing on the role of integrin co-receptors.

Main Results:

• α-defensins facilitated HAdV binding to cells even when primary receptors were absent or blocked.
• This defensin-mediated binding was independent of known viral receptors and co-receptors but remained integrin-dependent for infection.
• HAdV tropism was expanded to non-susceptible cells in the presence of α-defensins, suggesting a parallel binding pathway.

Conclusions:

• A novel HAdV binding pathway exists, mediated by α-defensins, that bypasses canonical viral receptors.
• This pathway converges on integrins for productive infection, functioning in parallel with receptor-mediated entry.
• α-defensins can significantly alter HAdV tropism in vivo, potentially making integrin expression a key determinant in certain tissues.