Data from: Alpha-defensin binding expands human adenovirus tropism

Mammalian α-defensins are a family of abundant effector peptides of the
mucosal innate immune system. Although primarily considered to be
antimicrobial, α-defensins can increase rather than block infection by
certain prominent bacterial and viral pathogens in cell culture and in
vivo. We have shown previously that exposure of mouse and human
adenoviruses (HAdVs) to α-defensins is able to overcome competitive
inhibitors that block cell binding, leading us to hypothesize a
defensin-mediated binding mechanism that is independent of known viral
receptors. To test this hypothesis, we used genetic approaches to
demonstrate that none of several primary receptors nor integrin
co-receptors are needed for human α-defensin-mediated binding of HAdV to
cells; however, infection remains integrin dependent. Thus, our studies
have revealed a novel pathway for HAdV binding to cells that bypasses
viral primary receptors. We speculate that this pathway functions in
parallel with receptor-mediated entry and contributes to
α-defensin-enhanced infection of susceptible cells. Remarkably, we also
found that in the presence of α-defensins, HAdV tropism is expanded to
non-susceptible cells, even when viruses are exposed to a mixture of both
susceptible and non-susceptible cells. Therefore, we propose that in the
presence of sufficient concentrations of α-defensins, such as in the lung
or gut, integrin expression rather than primary receptor expression will
dictate HAdV tropism in vivo. In summary, α-defensins may contribute to
tissue tropism not only through the neutralization of susceptible viruses
but also by allowing certain defensin-resistant viruses to bind to cells
independently of previously described mechanisms.