Higher viremia and pathogenesis of human adenovirus 7 is likely associated to enhanced disruption of junction integrity

The clinical effects of pediatric human adenovirus (HAdV) 7 infection are more severe than those caused by HAdV-3. This increased pathogenesis is likely associated with a higher viremia, i.e., a higher presence of HAdV-7 in blood, but the mechanisms that explain this are poorly understood. Herein, we tested the polarization of entry and release for both HAdV-7 or HAdV-3 in epithelial and endothelial cells, and evaluated the effect of these viruses on cellular junctions of epithelial cells, measuring transepithelial electrical resistance and paracellular flux. We show that epithelial cells are infected by both viruses via either basolateral or apical sides, but are released apically. In contrast, in endothelials cells, both entry and release can occur from either side. The replication capacity was higher for HAdV-7 than for HAdV-3, and infection led to more severe epithelial barrier damage, compromising tight junction integrity. These effects may be related to the higher viremia observed previously in HAdV-7. The way in which HAdV-7 traverses epithelial and endothelial barriers to establish a new infection offers new perspectives to treat its pathogenicity.