The mechanism of anterograde transport of alphaherpesviruses in axons remains controversial. This study examined the transport, assembly, and egress of herpes simplex virus type 1 (HSV-1) in mid-and distal axons of infected explanted human fetal dorsal root ganglia using confocal microscopy and transmission electron microscopy (TEM) at 19, 24, and 48 h postinfection (p.i.). Confocal-microscopy studies showed that although capsid (VP5) and tegument (UL37) proteins were not uniformly present in axons until 24 h p.i., they colocalized with envelope (gG) proteins in axonal varicosities and in growth cones at 24 and 48 h p.i. TEM of longitudinal sections of axons in situ showed enveloped and unenveloped capsids in the axonal varicosities and growth cones, whereas in the midregion of the axons, predominantly unenveloped capsids were observed. Partially enveloped capsids, apparently budding into vesicles, were observed in axonal varicosities and growth cones, but not during viral attachment and entry into axons. Tegument proteins (VP22) were found associated with vesicles in growth cones, either alone or together with envelope (gD) proteins, by transmission immunoelectron microscopy. Extracellular virions were observed adjacent to axonal varicosities and growth cones, with some virions observed in crescent-shaped invaginations of the axonal plasma membrane, suggesting exit at these sites. These findings suggest that varicosities and growth cones are probable sites of HSV-1 envelopment of at least a proportion of virions in the midto distal axon. Envelopment probably occurs by budding of capsids into vesicles with associated tegument and envelope proteins. Virions appear to exit from these sites by exocytosis.In humans, herpes simplex virus type 1 (HSV-1) enters via the mucosa or breaks in the skin. After replication in the epithelial cells, the virions infect the nerve endings of dorsal root ganglion (DRG) neurons innervating the infected tissue. The virus is then transported via retrograde axonal transport to the neuronal-cell body, where a lifelong latent infection is established. Reactivation of HSV-1 from latency results in anterograde axonal transport of the virus from the cell body to the nerve terminals to reinfect cells in the skin or mucosa. Reactivation of HSV-1 during a patient's lifetime is frequent, resulting in either recurrent symptomatic disease or asymptomatic virus shedding (45, 52).For many years, there has been controversy about the mechanism of assembly and egress of alphaherpesviruses in cultured cell lines. Until recently, there were two opposing models to explain the events following capsid assembly in the nucleus and subsequent budding through the inner nuclear membrane. The first model proposes that there is direct transport of enveloped capsids within vesicles from the outer nuclear membrane via the trans-Golgi network to the plasma membrane, where they are released by exocytosis (8,24). The second model proposes that enveloped capsids undergo de-envelopment at the outer nuclear membrane and ...

These results suggest that early diagnosis and treatment within 3 days of the onset of paralysis are necessary for maximal efficacy of combined acyclovir and prednisolone therapy for Bell's palsy.

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