Flavivirus Infection Enhancement in Macrophages: Radioactive and Biological Studies on the Effect of Antibody on Viral Fate

Abstract

35S-labeled West Nile virus was used in radioactive binding, internalization and degradation studies in the macrophage cell line P388D1 in the absence or presence of various concentrations of antiviral antibody. Proteases were used to help distinguish between intracellular and extracellular (bound) virus. It was found that the enhancement in viral infectivity that occurs in the presence of subneutralizing concentrations of antiviral antibody was caused by increased binding of virus to the cell surface and a higher specific infectivity of antibody-opsonized virus particles, apparently due to a more efficient internalization process. Little difference was found in the rate of internalization and intracellular degradation for virus particles that did enter the cells. Lysosomotropic amines were capable of markedly inhibiting viral replication in P388D1 cells at an early stage of infection both in the absence and presence of subneutralizing concentrations of antibody, although antibody-mediated enhancement of viral replication remained.