Progeny Varicella-Zoster Virus Capsids Exit the Nucleus but Never Undergo Secondary Envelopment during Autophagic Flux Inhibition by Bafilomycin A1

Girsch, James H.; Walters, Katherine; Jackson, Wallen; Grose, Charles

The second conclusion of our BAF studies involves the increased number of MVBs in BAF-treated cells. Investigators in an early study of the origins of MVBs in an animal model (which did not use BAF) concluded that the vesicles inside MVBs can be derived from vesicles found along the convex surface of the trans-Golgi cisternae (38) . A second group reported that drug-induced disorganization of the Golgi apparatus leads to the release of vesicles mainly from the trans-Golgi apparatus (39) . A third group documented an increased number of MVBs in cells treated with BAF (40, 41) . Specifically, they state that BAF treatment led to a noticeable decline in lysosomes and an increase in multivesicular endosomes. In our transmission electron micrographs, the morphology of the MVBs closely resembled those described by Friend (38) and Mousavi et al. (40) . In short, when we examined BAF-treated uninfected and infected cells, we confirmed the prior observation that BAF treatment by itself led to an increased presence of MVBs. We did not include this pathway in Fig. 8 , but it would involve entry of Golgi apparatus-derived vesicles released by a disorganized Golgi apparatus secondary to BAF treatment into an endosome by the endosomal sorting complexes required for transport (ESCRT) to form an MVB. Because of the BAF treatment, subsequent fusion of the MVB with a lysosome is blocked.