Comparative analysis of adenovirus fiber-cell interaction: Adenovirus type 2 (Ad2) and Ad9 utilize the same cellular fiber receptor but use different binding strategies for attachment

We have analyzed the binding of adenovirus (Ad) serotypes from subgroups B, C, and D through fiber-virus and fiber-fiber cross-competition experiments. Since viruses in these distinct subgroups display markedly different tropisms, it was unexpected that the subgroup C viruses Ad2 and 5 and the subgroup D virus Ad9 cross-competed for the same cellular fiber receptor. The subgroup B serotype Ad3 recognized a receptor distinct from the Ad2, 5, and 9 fiber receptor. However, despite sharing the same fiber receptor, Ad2 and Ad9 displayed markedly different binding characteristics that appeared to result from direct Ad9 binding to cells via alpha(v)-integrins. Unlike Ad2, Ad9 binding to many cell lines was not abrogated by competition with the fiber 9 knob (F9K). Ad9 binding to fiber receptor-deficient cells was blocked by a monoclonal antibody to alpha(v)-integrins, In contrast, Ad9 binding to alpha(v)-deficient cells that express fiber receptor was blocked by F9K. Transfection of an alpha(v)-integrin-deficient cell line with a plasmid that expresses alpha(v) beta(d) resulted in Ad9 binding that was not significantly blocked by F9K but was blocked with a combination of F9K and penton base. These results imply that the shorter length of fiber 9 (37 nm) relative to fiber 2 (37 nm) permits fiber-independent binding of Ad9 penton base to alpha(v)-integrins. The difference in fiber length may explain the different binding characteristics and tissue tropisms of each virus despite both utilizing the same fiber and penton base receptors.