Alpha-defensin binding expands human adenovirus tropism

Area of Science:

• Immunology
• Virology
• Cell Biology

Background:

• Mammalian alpha-defensins (α-defensins) are key innate immune peptides.
• While typically antimicrobial, α-defensins can paradoxically promote certain viral infections.
• Adenoviruses (HAdVs) are significant human pathogens.

Purpose of the Study:

• To investigate the mechanism by which α-defensins enhance HAdV infection.
• To determine if α-defensins mediate HAdV binding independently of known viral receptors.
• To explore the impact of α-defensins on HAdV tropism.

Main Methods:

• Genetic approaches were used to assess the role of viral receptors and co-receptors in α-defensin-mediated HAdV binding.
• Cell culture experiments were performed to observe HAdV binding and infection in the presence of α-defensins.
• Experiments evaluated HAdV tropism in mixed cell populations exposed to α-defensins.

Main Results:

• Human α-defensin-mediated binding of HAdV to cells did not require primary receptors or integrin co-receptors.
• However, HAdV infection remained dependent on integrins.
• α-defensins expanded HAdV tropism to non-susceptible cells, even in mixed cell environments.

Conclusions:

• A novel HAdV binding pathway exists, bypassing canonical viral receptors and operating in parallel with receptor-mediated entry.
• This pathway contributes to α-defensin-enhanced HAdV infection.
• In vivo, α-defensin presence may shift HAdV tissue tropism determination from primary receptor expression to integrin expression, particularly in mucosal tissues like the lung and gut.