Editors' ChoiceExcitability

Creepy Viruses Get Rid of All the Excitement

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Science's STKE  08 Oct 2002:
Vol. 2002, Issue 153, pp. tw362-TW362
DOI: 10.1126/stke.2002.153.tw362

Reactivation of latent infections with herpes simplex virus type-1 (HSV-1), a neurotropic virus that targets sensory ganglia and causes cold sores, is associated with loss of sensation and tingling parasthesia around the original infection site that results from a reduction in the excitability of infected neurons. Storey et al. demonstrate a selective internalization of voltage-activated sodium channels in sensory neurons infected with HSV-1 that underlies this loss of excitability and may represent a previously unknown pathway for regulating sensory neuron activity. Using voltage-clamp analysis of dissociated rat dorsal root ganglion neurons, the authors found decreased tetrodotoxin-sensitive and -insensitive sodium current 24 to 48 hours after infection of the cells with HSV-1. Calcium and potassium currents were unaffected. The remaining sodium current showed no change in the voltage dependence of activation or steady-state inactivation, suggesting a loss of functional sodium channels. Immunofluorescent analysis demonstrated a decrease in both plasma membrane and total sodium channel density. Pharmacological analysis indicated that the HSV-1-mediated reduction in sodium current depended on endocytosis and required the expression of viral late proteins, but not viral encapsulation or egress. HSV-1 mutants that lacked the HSV-1 neurovirulence factor, infected cell protein 34.5, had no effect on sodium current. The authors concluded that HSV-1-induced internalization and degradation of sodium channels was responsible for the loss of sensory neuron excitability, and suggested that this represented HSV-1 interaction with a novel pathway mediating dynamic control of sensory neuron excitability.

N. Storey, D. Latchman, S. Bevan, Selective internalization of sodium channels in rat dorsal root ganglion neurons infected with herpes virus-1. J. Cell Biol. 158, 1251-1262 (2002). [Abstract] [Full Text]

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