Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

Logo for

J. Cell Biol. 158 (7): 1251-1262

Copyright © 2002 by the Rockefeller University Press.


Article

Selective internalization of sodium channels in rat dorsal root ganglion neurons infected with herpes simplex virus-1

Nina Storey1, David Latchman2, and Stuart Bevan1

1 Novartis Institute for Medical Sciences, London WC1E 6BS, UK
2 Windeyer Department of Molecular Pathology, University College London Medical School, The Windeyer Institute of Medical Sciences, London W1P 6DB, UK

Address correspondence to Nina Storey at her present address, National Institute of Environmental Health Sciences, 111 Alexander Dr., PO Box 12233, Mail Drop F205, Research Triangle Park, NC 27709. Tel.: (919) 541-0287. Fax: (919) 541-1431. E-mail: storey{at}niehs.nih.gov

Abstract: 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.

Key Words: voltage-gated sodium channels; sensory neurons; sodium channel regulation; calcium channels; potassium channels


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Selective Changes in Human Corneal Sensation Associated with Herpes Simplex Virus Keratitis.
J. Gallar, T. M. T. Tervo, W. Neira, J. M. Holopainen, M. E. Lamberg, F. Minana, M. C. Acosta, and C. Belmonte (2010)
Invest. Ophthalmol. Vis. Sci. 51, 4516-4522
   Abstract »    Full Text »    PDF »
Role of the NH2 Terminus in the Assembly and Trafficking of the Intermediate Conductance Ca2+-activated K+ Channel hIK1.
H. M. Jones, K. L. Hamilton, G. D. Papworth, C. A. Syme, S. C. Watkins, N. A. Bradbury, and D. C. Devor (2004)
J. Biol. Chem. 279, 15531-15540
   Abstract »    Full Text »    PDF »
Latent Herpes Simplex Virus Infection of Sensory Neurons Alters Neuronal Gene Expression.
M. F. Kramer, W. J. Cook, F. P. Roth, J. Zhu, H. Holman, D. M. Knipe, and D. M. Coen (2003)
J. Virol. 77, 9533-9541
   Abstract »    Full Text »    PDF »

To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882