Removal of Cell-Associated Myxoviruses by Antibody 1

Abstract

Discussion and Summary

The fact that the two strains IS and BA in AL showed such a large difference in sensitivity to the same NDV antibody makes it seem likely that the disappearance of cell-associated viral hemagglutinins is due to a reaction at the cell membrane, not inside the cell. Since the HAI titer was approximately the same for IS as for BA, entry of antibody into the cell should cause equal inhibition. In the antibody-sensitive cell-virus systems, virus budding through the membrane probably is removed as fast as it is formed and it follows that maturation is exclusively at a site accessible to antibody. With virus strains where large amounts of cell associated hemagglutinins are formed, even in the presence of extracellular antibody, intracellular HA production seems likely. Evidence for association of influenza virus with internal membranes of the cell has been presented by Holland and Kiehn (8). Also it is of interest that ascites lymphoma cells infected with influenza are more resistant to antiviral immune cytolysis, early or late in infection, than are those infected with Sendai or NDV (9). Part of the increased resistance in CE might be attributed to small clumps of cells which were difficult to eliminate from the suspensions. For example, NDV-IS, highly sensitive in AL, was resistant in CE. However, Sendai was inhibited by about the same antibody concentration in either cell species and WSN was apparently more resistant in AL than in CE.

Resistance was overcome by increasing the antibody concentration. In CE, the strains NDV-IS, NDV-BA, and influenza, became sensitive to high antibody levels. An explanation of this phenomenon must await further investigation but concentration dependence suggests forced diffusion across a barrier. The alternative is entrance of small amounts of antibody into the cell through pinocytosis.

The action of antibody at 24 hr in causing disappearance of cell-associated HA does not seem related to cell disruption by the virus, at least those cases where dye exclusion remained effective or the inhibition was reversible.