page 1251, Storey et al. describe the molecular mechanism responsible for this phenomenon. Their findings may also be relevant to the normal rearrangements of voltage-dependent sodium channels that occur during neuronal development.
The authors found that neurons from the rat dorsal root ganglion show a profound and rapid loss of voltage-dependent sodium currents ∼24 h after infection with HSV-1. Loss of excitability in these neurons correlates with the loss of sodium channels from the cell surface. Blocking endocytosis or preventing the production of HSV-1 late proteins prevents the loss of excitability, and a mutant virus lacking the neuro-virulence factor ICP 34.5 does not cause the loss of sodium channels seen in wild-type viral infections.Previous work has shown that HSV-1 modifies the ubiquitin–proteasome pathway, leading to the destruction of many cellular proteins, and this may also explain the internalization of sodium channels. If the virus is tapping into a normal cellular pathway, then the same ubiquitin–proteasome pathway may also explain the rapid disappearance of sodium channels at nodes of Ranvier during development. ▪