Evidence that Sindbis virus infects BHK-21 cells via a lysosomal route

Chloroquine and NH4Cl, potent inhibitors of lysosomal function, decreased the production of infectious Sindbis virus particles in BHK-21 cells by 10- and 12-fold, respectively. There were no apparent toxic effects on cells exposed to these lysosomotropic agents. These chemicals did not alter the rate of cellular protein synthesis, with the exception of a reversible twofold inhibition by chloroquine. No additive effects of chloroquine and NH4Cl were observed when the cells were saturated with these weak bases, which suggests that their effect is exerted via the same mechanism, most likely as a result of an increase in lysosomal pH. The reduction in the formation of Sindbis virions was monitored by incorporation of [35S]methionine and shown to be fourfold by chloroquine or NH4Cl at 5 h postinfection but negligible at 11 h postinfection. These results strongly suggest that a productive Sindbis virus infection requires functional lysosomes. Thus, endocytosis is probably the main infectious mechanism for penetration of this virus into BHK-21 cells.