Vitronectin: A Poible Determinant of Adenoviru Type 19 Tropim for Human Corneal Epithelium

Purpoe Adenovirue typically demontrate pecific tiue tropim, a in the aociation of Ad19 with epidemic keratoconjunctiviti. We ought to determine factor that might influence the apparent tropim of Ad19 for the cornea. Deign Laboratory invetigation. Method Adenoviru erotype Ad2, 5, 9, 10, 11, 13, and 19 were compared for their capacity to replicate in human corneal epithelial cell (HCEC) in culture. Organotypically cultured human cornea were infected with Ad19 or Ad2, and viral titer were compared after 7 day. Replication of both virue wa compared in HCEC cultured on variou extracellular matrice. Wetern blot analyi and immunohitochemitry were applied to human donor cornea and HCEC. Reult One week after infection of HCEC monolayer culture, Ad2 titer were ignificantly higher than any of the other virue teted (P <.05). In organotypic corneal culture, Ad19 titer were ignificantly higher than Ad2 (P = .0003). Ad2 replication in HCEC equaled or exceeded that of Ad19 on all extracellular matrice except vitronectin, where Ad2 replication wa reduced and Ad19 replication enhanced (P <.0001). Vitronectin wa detected by immunohitochemitry within the corneal epithelial baement membrane of human donor cornea. Increaed αv integrin expreion and greater tyroine kinae phophorylation in HCEC cultured on vitronectin were demontrated by Wetern blot analyi. Concluion In vitro, vitronectin enhance growth of Ad19, poibly by up-regulation of receptor αv integrin and increaed activity of tyroine kinae neceary for adenoviral internalization. We hypotheize that differential tiue tropim for adenovirue may derive in part from tiue-pecific extracellular matrix expreion.