Anterograde transport of herpes simplex virus type 1 in cultured, dissociated human and rat dorsal root ganglion neurons

The mechanism of anterograde transport of herpes simplex virus was studied in cultured dissociated human and rat dorsal root ganglion neurons. The neu rons were infected with HSV-1 to examine the distribution of capsid (VP5), tegument (VP16), and glycoproteins (gC and gB) at 2, 6, 10, 13, 17, and 24 h postinfection (p.i.) with or without nocodazole (a microtubule depolymeri zer) or brefeldin A (a Golgi inhibitor). Retrogradely transported VP5 was d etected in the cytoplasm of the cell body up to the nuclear membrane at 2 h p.i, It was first detected de novo in the nucleus and cytoplasm at 10 h p. i., the axon hillock at 13 h p.i., and the axon at 15 to 17 h p.i. gC and g B were first detected de novel in the cytoplasm and the axon hillock at 10 h p.i., and then in the axon at 13 h p.i., which was always earlier than th e detection of VP5. De novo-synthesized VP16 was first detected in the cyto plasm at 10 to 13 h p.i. and in the axon at 16 to 17 h p.i. Nocodazole inhi bited the transport of all antigens, VP5, VP16, and gC or gB. The kinetics of inhibition of VP5 and gC could be dissociated. Brefeldin A inhibited the transport of gC or gB and VP16 but not VP5 into axons, Transmission immuno electron microscopy confirmed that there were unenveloped nucleocapsids in the axon with or without brefeldin A. These findings demonstrate that glyco proteins and capsids, associated with tegument proteins, are transported by different pathways with slightly differing kinetics from the nucleus to th e axon. Furthermore, axonal anterograde transport of the nucleocapsid can p roceed despite the loss of most VP16.