INHIBITION BY BREFELDIN-A OF THE ENVELOPMENT OF NUCLEOCAPSIDS IN HERPES-SIMPLEX VIRUS TYPE 1-INFECTED VERO CELLS

Inhibition by Brefeldin A (BFA) of the multiplication of herpes simplex virus (HSV) type 1 in Vero cells was characterized quantitatively. The yield of infectious progeny virus decreased exponentially with increasing concentrations of BFA while the yield of enveloped virus particles decreased less steeply to the level of approximately one fifth of the yield in the untreated cells; the level then remained constant even at higher BFA concentrations. The yield of nucleocapsids was not markedly affected by the drug. These results suggest that there are two different (i.e., BFA-sensitive and -insensitive) pathways for the formation of enveloped particles in the HSV-1-infected cells and that the infectious progeny virus arises exclusively from the BFA-sensitive pathway. Addition of BFA at various times after infection showed that the agent inhibited the increase in the amount of enveloped particles and of infectious progeny virus immediately after the addition. Single-step growth experiments suggested that, even in the presence of mature viral envelope proteins and of nucleocapsids, the increase in the amount of enveloped particles was completely inhibited by the addition of BFA at a late stage of infection. These results are consistent with the concept that the Golgi complex, the most BFA-sensitive organelle, is the major envelopment site of HSV-1 nucleocapsids leading to the formation of the infectious progeny virus.