west nile virus infection causes endocytosis of a specific subset of tight junction membrane proteins西尼罗河病毒感染导致的内吞作用紧密连接膜蛋白的特定子集.pdfVIP

West Nile Virus Infection Causes Endocytosis of a Specific Subset of Tight Junction Membrane Proteins 1 2 1 3 1,4,5 Zaikun Xu , Regula Waeckerlin , Matt D. Urbanowski , Guido van Marle , Tom C. Hobman * 1 Department of Cell Biology, Li Ka Shing Institute of Virology, University of Alberta, Edmonton, Alberta, Canada, 2 Department of Ecosystems and Public Health, University of Calgary, Alberta, Canada, 3 Department of Microbiology, Immunology and Infectious Diseases, University of Calgary, Alberta, Canada, 4 Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta, Canada, 5 Li Ka Shing Institute of Virology, University of Alberta, Edmonton, Alberta, Canada Abstract 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 GTP