bafilomycin-a1 and African-Swine-Fever

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.

Topics: Acridine Orange; African Swine Fever; African Swine Fever Virus; Amantadine; Animals; Anti-Bacterial Agents; Antiviral Agents; Cells, Cultured; Chloroquine; Cytoplasm; Enzyme Inhibitors; Female; Fluorescein-5-isothiocyanate; Hydrogen-Ion Concentration; Lysosomes; Macrolides; Macrophages; Male; Proton Pump Inhibitors; Proton Pumps; Proton-Translocating ATPases; Swine; Vacuoles; Virus Replication; Zymosan