Macrophage cytoplasmic vesicle pH gradients and vacuolar H+-ATPase activities relative to virus infection.

ABSTRACT

A number of viruses replicate in macrophages, some having an obligate requirement for a macrophage host. This raised the question concerning the role of the macrophage endosomal/lysosomal compartment during such infections. Both lysosomotropic weak bases, amantadine and chloroquine, which interfere with endosomal/lysosomal pH gradients, and the macrolide antibiotic bafilomycin A1, which interferes with vacuolar H+-ATPase, inhibited African swine fever (ASF) virus replication in porcine macrophages. This inhibition was reversible replenishment of bafilomycin, but not amantadine or chloroquine, maintained the inhibition. The characteristics of the inhibition, and the capacity of virus to escape and re-commence replication, related to the capacity of each drug to interfere with the endosomal/lysosomal proton pump. These results demonstrate that the virus actually requires macrophage endosomal/lysosomal activity for its replication. Therein, vacuolar H+-ATPase activity is particularly critical for successful virus replication, which is interesting considering the importance of this for endosomal/lysosomal activity and macrophage function.