Effect of lysosomotropic compounds on early events in XXXX virus replication.

@entity6193 @entity8777 @entity4021 @entity281 @entity503
The effect of three lysosomotropic compounds, @entity503 , @entity6193 and @entity8777 , on the replication of @entity4021 virus (FMDV) type A12 was studied. Viral replication was almost totally inhibited by 0.5 mM @entity503 , 50 microM @entity6193 , or 25 mM @entity8777 . @entity6193 and @entity8777 affected replication when added either before or within the first hour of @entity281 . @entity503 , however, still inhibited viral replication when added up to 2.5 h after @entity281 . Assays of binding of radiolabeled virus to cells showed that these compounds had no effect on viral adsorption. Neither @entity6193 nor @entity8777 had any significant effect on cellular protein synthesis, but there was no evidence of viral protein synthesis in cells infected in the presence of these compounds. In contrast, @entity503 inhibited both cellular and viral protein synthesis. Eclipse assays, performed in the presence of the compounds, showed that while @entity503 and @entity8777 had little effect on cell-induced degradation of incoming virions to 12 S protein subunits, @entity6193 inhibited this reaction. The replication of representative members of all seven serotypes of FMDV was inhibited by @entity6193 although some types were less sensitive to the compound than others. These results are consistent with a model which postulates that viral eclipse is the result of acidification of endocytic vesicles which degrade entrapped virions to 12 S protein subunits resulting in the release of genome RNA.
