Foot-and-mouth disease virus undergoes restricted replication in macrophage cell cultures following Fc receptor-mediated adsorption

Abstract

We have previously reported that foot-and-mouth disease virus (FMDV) can enter an Fc receptor (FcR)-expressing cell line by antibody-dependent enhancement. Since FMDV can establish a persistent infection in animals in the presence of high levels of neutralizing antibodies (carrier state), we examined macrophages for their ability to be infected by the virus in the presence of antibody. The murine macrophage cell line P388D1 or porcine macrophage-monocytes isolated from peripheral blood were incubated with antibody-complexed virus. Under these conditions, host protein synthesis was rapidly inhibited in both cell types, but not in cells incubated either with virus alone or with imine-inactivated antibody-complexed virus. Virus-specific structural and nonstructural proteins were synthesized in antibody-complexed virus-infected P388D1 cells, while only nonstructural proteins were detected in porcine macrophage cultures. Negative-strand RNAs were detected in both cell types, indicating that RNA replication had taken place. Cultures of P388D1 cells transfected with viral RNA produced very low levels of infectious virus, and infection with virus-antibody complexes, followed by a brief wash with pH 6.0 buffer to remove residual input virus, allowed the detection of low levels of productive replication. Thus, macrophages can be infected with FMDV via FcR-mediated adsorption, and infection of these cells could contribute to pathology or provide a reservoir of infectious virus in carrier animals.