Mechanisms of neutralization of influenza virus in tracheal epithelial and BHK cells vary according to IgG concentration

Abstract

The interaction of IgG-neutralized type A influenza virus with differentiated epithelial cells of mouse trachea, BHK cells, and chicken erythrocytes was studied using three mouse monoclonal antibodies (IgG2a) each directed against a different antigenic site on the hemagglutinin. At high HIU:HAU ratios virus was neutralized >99%, monodisperse, and attached to tracheal epithelial and BHK cells in normal amounts. The majority (70–80%) of neutralized virus failed to attach to erythrocytes. At low HIU:HAU ratios the virus was aggregated by each of the antibodies, and attachment to tracheal epithelial and BHK cells was inhibited by up to 75%. Combined aggregation and inhibition of attachment could theoretically account for up to 96% loss of infectivity but this corresponded with the observed degree of neutralization with only one of the antibodies. With increasing antibody:virus ratios, aggregation and inhibition of attachment contributed ever diminishingly to the observed neutralization and eventually not at all. Both neutralized and infectious virus attached to neuraminidase-sensitive receptors. After attachment neutralized virus became increasingly resistant to removal by neuraminidase suggesting that it had been internalized by the cell.