Monoclonal anti-Fc receptor IgG blocks antibody enhancement of viral replication in macrophages

Flaviviruses, when complexed with antibody at subneutralizing concentrations, show enhanced replication in human and simian peripheral blood leukocytes (ref. 1, and J.S.M.P. and J.S.P., unpublished observations) and in P388 D1 and other macrophage cell lines². A comparable phenomenon has been demonstrated with alphaviruses and Bunyaviruses in P388 D1 cells, (J.S.M.P. and J.S.P., unpublished observations) but cells lacking macrophage characteristics fail to show antibody-dependent enhancement (ADE) of viral replication. It has been suggested that the macrophage Fc receptor (FcR) providesan efficient route of entry of virus through the attachment of non-neutralized virus-antibody complexes and that for those viruses that escape destruction by the phagocyte, antibody results in a paradoxical increase in virus replication³. West Nile virus (WNV) replication in the P388 D1 macrophage cell line provides a reproducible model system for studying ADE of viral replication.Mouse macrophages have two FcRs - FcRI, which is trypsin-sensitive and binds IgG2a, and FcRII, which is trypsin-resistant and binds IgG2b and IgG1 complexes⁴. The FcR has been purified ⁵ using rat anti-mouse FcR monoclonal antibody which blocks FcRII⁶. We show here that anti-FcR IgG and its Fab fragment block ADE of virus replication by anti-WNV monoclonal antibodies.