West Nile virus infection causes endocytosis of a specific subset of tight junction membrane proteins.
West Nile virus (WNV) is a blood-borne pathogen that causes systemic infections and serious neurological disease in human and animals. The most common route of infection is mosquito bites and therefore, the virus must cross a number of polarized cell layers to gain access to organ tissue and the central nervous system. Resistance to trans-cellular movement of macromolecules between epithelial and endothelial cells is mediated by tight junction complexes. While a number of recent studies have documented that WNV infection negatively impacts the barrier function of tight junctions, the intracellular mechanism by which this occurs is poorly understood. In the present study, we report that endocytosis of a subset of tight junction membrane proteins including claudin-1 and JAM-1 occurs in WNV infected epithelial and endothelial cells. This process, which ultimately results in lysosomal degradation of the proteins, is dependent on the GTPase dynamin and microtubule-based transport. Finally, infection of polarized cells with the related flavivirus, Dengue virus-2, did not result in significant loss of tight junction membrane proteins. These results suggest that neurotropic flaviviruses such as WNV modulate the host cell environment differently than hemorrhagic flaviviruses and thus may have implications for understanding the molecular basis for neuroinvasion.
Department of Cell Biology, Li Ka Shing Institute of Virology, University of Alberta, Edmonton, Alberta, Canada.
Zaikun
Z
Xu
Regula
R
Waeckerlin
Matt D
MD
Urbanowski
Guido
G
van Marle
Tom C
TC
Hobman
D000818:Animals; D018938:Caco-2 Cells; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002460:Cell Line; D062445:Claudin-1; D034281:Dynamins / Q000378:metabolism; D004705:Endocytosis; D042783:Endothelial Cells / Q000378:metabolism / Q000821:virology; D004847:Epithelial Cells / Q000378:metabolism / Q000821:virology; D057809:HEK293 Cells; D054884:Host-Pathogen Interactions; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism / Q000821:virology; D019108:Tight Junctions / Q000378:metabolism / Q000821:virology*; D014901:West Nile Fever / Q000378:metabolism / Q000821:virology*; D014902:West Nile virus / Q000502:physiology*
C568108:CLDN1 protein, human; D015815:Cell Adhesion Molecules; D062445:Claudin-1; D008565:Membrane Proteins; D034281:Dynamins