Parainfluenza viruses are a common cause of seasonal respiratory disease, but in high-risk individuals (e.g., young children) these viruses can cause severe clinical manifestations that require hospitalization.
Beta-defensins are a subclass of
antimicrobial peptides with
antiviral activity. Use of adenovirus-mediated
beta-defensin gene expression has been proposed as
therapy for chronic
bacterial infections commonly seen in
cystic fibrosis patients; however, its use during
parainfluenza virus 3 (PIV3)
infection has not been evaluated. The hypothesis in this experiment was that adenovirus expression of human
beta-defensin 6 (HBD6) would diminish concurrent PIV3
infection in neonatal lambs. The group infected with adenovirus HBD6 and PIV3 had increased levels of pulmonary neutrophil recruitment compared to those for the group infected with PIV3 or PIV3 and adenovirus, with an increased respiration rate and body temperature late in the course of the PIV3-adenovirus HBD6
infection. Interestingly, the adenovirus-treated groups had higher levels of immunohistochemical staining for PIV3 and syncytial cell formation than the group infected with PIV3, suggesting that treatment with the adenovirus vector, regardless of whether it was carrying a target gene, exacerbated the PIV3
infection. The levels of expression of
mRNA for antimicrobial
surfactant proteins A and D and sheep
beta-defensin 1 were increased by PIV3 and adenovirus treatment, and the increased levels of expression roughly corresponded to the degree of
inflammation. While pulmonary administration of a high-dose adenovirus vector has been associated with undesirable
inflammation, this is the first study to show that it can exacerbate concurrent
viral infection, a concern that needs to be addressed for future studies of adenovirus in the lung. Additionally, this study showed that adenovirus-mediated HBD6 expression increases neutrophil recruitment, a recently described attribute of
beta-defensins, with mild accentuation of PIV3 activity and
inflammation.