A HUMAN CELL-LINE SELECTED FOR RESISTANCE TO ADENOVIRUS INFECTION HASREDUCED LEVELS OF THE VIRUS RECEPTOR

To investigate determinants of host cell susceptibility to infection, cells partially resistant to infection were selected from the rare cel ls which remained adherent after infection of a culture of A549 cells with Ad2RAE, a mutant of adenovirus type 2 whose vertex capsomers lack an Arg-Gly-Asp (RGD) sequence which mediates binding of wild-type vir us to integrins. Integrins promote the internalization of attached vir ions, whereas adsorption itself results from binding of the viral fibe rs to an unidentified cellular receptor, Following three rounds of sel ection, a persistently infected culture was established in which virus replication was detected in approximately 5% of the cells, Uninfected cells were readily cloned from the culture, indicating that at any pa rticular time the majority of cells in the culture were uninfected, Th e resistance of one clone of uninfected cells to infection was correla ted with a 10-fold reduction in the concentration of fiber receptors o n these cells compared with the parental A549 cell line, indicating th at efficiency of virus adsorption depends on the receptor concentratio n, Surprisingly, the rate at which host cells internalized RGD-negativ e virus also was strongly dependent on the fiber receptor concentratio n. While internalization of wild-type virus is promoted by the binding of integrins to the penton base RGD sequence, these results suggest t hat virus also can enter cells by an alternate pathway which requires binding of virions to multiple fiber receptors.