Macrophage cytoplasmic vesicle pH gradients and vacuolar H+-ATPase activities relative to virus infection.
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.[1]References
- Macrophage cytoplasmic vesicle pH gradients and vacuolar H+-ATPase activities relative to virus infection. Natale, V.A., McCullough, K.C. J. Leukoc. Biol. (1998) [Pubmed]
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