Details

Autor(en) / Beteiligte

• Storey, Nina
• Latchman, David
• Bevan, Stuart

Titel

Selective Internalization of Sodium Channels in Rat Dorsal Root Ganglion Neurons Infected with Herpes Simplex Virus-1

Ist Teil von

• The Journal of cell biology, 2002-09, Vol.158 (7), p.1251-1262

Ort / Verlag

United States: Rockefeller University Press

Erscheinungsjahr

2002

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• The neurotropic virus, herpes simplex type 1 (HSV-1), inhibits the excitability of peripheral mammalian neurons, but the molecular mechanism of this effect has not been identified. Here, we use voltage-clamp measurement of ionic currents and an antibody against sodium channels to show that loss of excitability results from the selective, precipitous, and complete internalization of voltage-activated sodium channel proteins from the plasma membrane of neurons dissociated from rat dorsal root ganglion. The internalization process requires viral protein synthesis but not viral encapsulation, and does not alter the density of voltage-activated calcium or potassium channels. However, internalization is blocked completely when viruses lack the neurovirulence factor, infected cell protein 34.5, or when endocytosis is inhibited with bafilomycin A1 or chloroquine. Although it has been recognized for many years that viruses cause cell pathology by interfering with signal transduction pathways, this is the first example of viral pathology resulting from selective internalization of an integral membrane protein. In studying the HSV-induced redistribution of sodium channels, we have uncovered a previously unknown pathway for the rapid and dynamic control of excitability in sensory neurons by internalization of sodium channels.