West nile virus capsid degradation of claudin proteins disrupts epithelial barrier function

Guruprasad R. Medigeshi, Alec J. Hirsch, James D. Brien, Jennifer L. Uhrlaub, Peter W. Mason, Clayton Wiley, Janko Nikolich-Zugich, Jay A. Nelson

Research output: Contribution to journalArticle

43 Scopus citations

Abstract

During acute infection, West Nile virus (WNV) has been reported to infect a variety of cell types in various tissues of both experimentally and naturally infected hosts. Virus infects epithelial cells in the skin, kidney, intestine, and testes, although the importance of these findings is unclear. In the current study, we have observed that WNV infection of kidney tubules in mice coincides with the loss of expression of several members of the claudin family. Proteins of this family are often involved in epithelial barrier formation and function. WNV infection of epithelial cells in culture resulted in a decrease in the transepithelial electrical resistance, an increase in the efflux of mannitol across the monolayer, and a loss of intracellular levels of claudin-1 to -4. WNV capsid alone was sufficient for the degradation event, which was mediated through lysosomal proteases. Since epithelial cells are frequent sites of WNV infection, these observations imply a potential mechanism for virus dissemination and extraneural pathogenesis.

Original languageEnglish (US)
Pages (from-to)6125-6134
Number of pages10
JournalJournal of virology
Volume83
Issue number12
DOIs
StatePublished - Jun 1 2009

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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    Medigeshi, G. R., Hirsch, A. J., Brien, J. D., Uhrlaub, J. L., Mason, P. W., Wiley, C., Nikolich-Zugich, J., & Nelson, J. A. (2009). West nile virus capsid degradation of claudin proteins disrupts epithelial barrier function. Journal of virology, 83(12), 6125-6134. https://doi.org/10.1128/JVI.02617-08