The HAdV-7 DNA-binding protein (DBP) increases viral infectivity and replication competence compared with HAdV-3

Human adenovirus type 7 (HAdV-7) causes more severe disease than HAdV-3. The adenoviral DNA binding protein (DBP) is a key regulatory protein involved in the viral replication cycle. However, the role of DBP in HAdV-7-induced severe disease remains poorly understood. rAd3E-7DBP was generated by replacing the DNA-binding protein (DBP) in recombinant HAdV-3 (rAd3E) with HAdV-7 DBP, and rAd7E-3DBP was constructed by replacing the DBP in recombinant HAdV-7 (rAd7E) with HAdV-3 DBP. We compared infectivity, cellular tropism, and replication competence between wild-type HAdV-3 and HAdV-7, and among recombinant strains rAd3E, rAd3E-7DBP, rAd7E-3DBP, and rAd7E, in human airway organoids.Wild-type HAdV-7 showed significantly higher infection rates and viral titers than HAdV-3. HAdV-7 infected more ciliated cells, club cells, basal cells, and goblet cells than HAdV-3 in human airway organoids. Additionally, compared with rAd3E, rAd7E infected more ciliated cells, basal cells, club cells, and goblet cells in human airway organoids. rAd7E infected more ciliated and basal cells than rAd7E-3DBP, whereas rAd3E infected fewer ciliated and basal cells than rAd3E-7DBP in human airway organoids. rAd7E showed significantly higher infection rates and viral titers than rAd3E in human airway organoids. rAd7E showed significantly higher infection rates and viral titers than rAd7E-3DBP, whereas rAd3E showed significantly lower infection rates and viral titers than rAd3E-7DBP in human airway organoids.This study suggest that HAdV-7 exhibited a significantly higher infection rate, cellular tropism, and replication competence than HAdV-3 in human airway organoids, and that these differences were due in large part to DBP.