MUTATIONS THAT ALTER AN ARG-GLY-ASP (RGD) SEQUENCE IN THE ADENOVIRUS TYPE-2 PENTON BASE PROTEIN ABOLISH ITS CELL-ROUNDING ACTIVITY AND DELAY VIRUS REPRODUCTION IN FLAT CELLS

The adenovirus penton base protein has a cell rounding activity and ma y lyse endosomes during virus entry into the cytoplasm. We found that penton base that was expressed in Escherichia coli also caused cell ro unding and that cells adhered to polystyrene wells that were coated wi th the protein. Mutant analysis showed that both properties required a n Arg-Gly-Asp (RGD) sequence at residues 340 to 342 of penton base. In flat adherent cells, virus mutants with amino acid substitutions in t he RGD sequence were delayed in virus reproduction and in the onset of viral DNA synthesis. In nonadherent or poorly spread cells, the kinet ics of mutant virus reproduction were similar to those of wild-type ad enovirus type 2. Expression of the mutant phenotype exclusively in the flat cells that we tested supports a model in which penton base inter acts with an RGD-directed cell adhesion molecule during adenovirus upt ake or uncoating.