Macrophage phagocytosis of foot-and-mouth disease virus may create infectious carriers

Macrophages play critical roles in innate defences against virus infections, particularly pertinent to the rapid immune response required following emergency vaccination against foot-and-mouth disease virus (FMDV). Consequently, macrophage-FMDV interaction was studied in vitro , in the absence of specific antibodies, to mimic the animal early postvaccination. A gradual loss of infectivity and viral antigen was observed over 48 hr, and no evidence of productive virus replication was found. From the pathological viewpoint, an important observation was that the majority of macrophages carried infectious virus for at least 10 hr. Pronase and mild acid treatments showed the virus to be primarily on the cell surface during the first 4 hr. Thereafter, it became internalized (pronase- and pH resistant), but remained infectious for 10-24 hr. The internalization process was dependent on microfilament activity, while the survival of infectious virus related to live virus-dependent inhibition of macrophage protein synthesis. Infectious centre assays demonstrated that this infectious virus - whether on the cell surface or internalized - was actually being released from the cells. This is interesting considering that FMDV is highly pH labile. Together, these characteristics suggest that the virus had been internalized by a process such as macropinocytosis, and fusion with endosomes was delayed or impaired. This mechanism whereby the virus could 'piggyback' on or in the macrophage, becoming internalized but not degraded for at least 10 hr, are important considerations in FMD pathogenesis. Such 'virus-transporting' macrophages would be in a position to carry infectious FMDV to different sites in the body, where it could be released to infect other cells for replication.