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)beta5 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 (11 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.
GenVec, Inc., Rockville, Maryland 20852, USA.
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Roelvink
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Kovesdi
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Wickham
D000260:Adenoviruses, Human / Q000378:metabolism*; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D001483:Base Sequence; D001665:Binding Sites; D001667:Binding, Competitive; D002213:Capsid / Q000378:metabolism*; D036022:Capsid Proteins; D002460:Cell Line; D006224:Cricetinae; D004279:DNA, Viral; D006367:HeLa Cells; D006801:Humans; D039564:Integrin alphaV; D016023:Integrins / Q000378:metabolism*; D008969:Molecular Sequence Data; D011991:Receptors, Virus / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D036022:Capsid Proteins; D004279:DNA, Viral; D039564:Integrin alphaV; D016023:Integrins; D011991:Receptors, Virus; C018315:hexon capsid protein, Adenovirus