Ezrin is essential for the entry of Japanese encephalitis virus into the human brain microvascular endothelial cells.

Emerging Microbes & Infections
Yan-Gang LiuZhongtian Qi

Abstract

Japanese encephalitis virus (JEV) remains the predominant cause of viral encephalitis worldwide. It reaches the central nervous system upon crossing the blood-brain barrier through pathogenic mechanisms that are not completely understood. Here, using a high-throughput siRNA screening assay combined with verification experiments, we found that JEV enters the primary human brain microvascular endothelial cells (HBMEC) through a caveolae-mediated endocytic pathway. The role of ezrin, an essential host factor for JEV entry based on our screening, in caveolae-mediated JEV internalization was investigated. We observed that JEV internalization in HBMEC is largely dependent on ezrin-mediated actin cytoskeleton polymerization. Moreover, Src, a protein predicted by a STRING database search, was found to be required in JEV entry. By a variety of pharmacological inhibition and immunoprecipitation assays, we found that Src, ezrin, and caveolin-1 were sequentially activated and formed a complex during JEV infection. A combination of in vitro kinase assay and subcellular analysis demonstrated that ezrin is essential for Src-caveolin-1 interactions. In vivo, both Src and ezrin inhibitors protected ICR suckling mice against JEV-induced mortalit...Continue Reading

References

Dec 22, 1999·Journal of Neurovirology·W M Pardridge
Jun 6, 2000·Journal of Biomolecular Screening·J H ZhangK R Oldenburg
Apr 25, 2003·Critical Reviews in Oncology/hematology·Tracey A MartinWen G Jiang
Jan 5, 2005·Biochemical and Biophysical Research Communications·Shue-Ling RaungChun-Jung Chen
Sep 1, 2007·Journal of Cellular and Molecular Medicine·P Lajoie, I R Nabi
Oct 4, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Anja RuppeltKjetil Taskén
Jan 8, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Christine LauChung-Wai Chow
Nov 26, 2008·Microvascular Research·Guochang Hu, Richard D Minshall
Jan 8, 2010·Journal of Virology·Hideki TaniYoshiharu Matsuura
Mar 4, 2010·Annual Review of Biochemistry·Jason MercerAri Helenius
Mar 24, 2010·Nature Reviews. Molecular Cell Biology·Richard G FehonAnthony Bretscher
Nov 16, 2011·Bulletin of the World Health Organization·Grant L CampbellAmy S Ginsburg
May 4, 2013·Journal of Cell Science·Yohei Yamauchi, Ari Helenius
Oct 18, 2013·Molecular Biology of the Cell·Efrat Gottlieb-AbrahamYoav I Henis
Oct 30, 2014·Nucleic Acids Research·Damian SzklarczykChristian von Mering
Aug 25, 2015·Molecular and Cellular Endocrinology·Katarzyna Chojnacka, Dolores D Mruk
Mar 11, 2017·Virus Research·Mazen M Jamil Al-ObaidiShamala Devi Sekaran
Jul 12, 2018·Expert Opinion on Biological Therapy·Luisa Barzon, Giorgio Palù
Aug 15, 2018·Pathogens·Sang-Im Yun, Young-Min Lee
Apr 16, 2019·Frontiers in Microbiology·Yasmin Mucunã MustafáLuciana Barros de Arruda
May 28, 2019·Emerging Microbes & Infections·Sheng-Lin ChenZhong-Tian Qi
Nov 30, 2019·F1000Research·Arup Banerjee, Aarti Tripathi
Dec 20, 2019·Emerging Infectious Diseases·Ryusei KuwataKen Maeda

❮ Previous
Next ❯

Citations

Sep 10, 2020·Innate Immunity·Zhuangzhuang Chen, Guozhong Li
Nov 27, 2020·Frontiers in Cell and Developmental Biology·Yanan SongWei Xia
Jun 26, 2021·Current Opinion in Virology·Carlos Daniel Cordero-RiveraRosa María Del Ángel
Jul 19, 2021·Molecular Aspects of Medicine·Kiran Bala SharmaManjula Kalia

❮ Previous
Next ❯

Methods Mentioned

BETA
transfection
confocal microscopy
immunoprecipitation
coimmunoprecipitation

Software Mentioned

GraphPad Prism
Search Tool for the Retrieval of Interacting Genes (
GraphPad

Related Concepts

Related Feeds

Blood Brain Barrier

The blood brain barrier is a border that separates blood from cerebrospinal fluid. Discover the latest search on this highly selective semipermeable membrane here.

Blood Brain Barrier Chips

The blood brain barrier (BBB) is comprised of endothelial cells that regulate the influx and outflux of plasma concentrations. Lab-on-a-chip devices allow scientists to model diseases and mechanisms such as the passage of therapeutic antibodies across the BBB. Discover the latest research on BBB chips here.

Caveolins & Signal Transduction

Caveolins are small proteins with a hairpin loop conformation that are located in the plasma membrane of various cell types where they bind cholesterol and interact with receptors essential for several signal transduction pathways. Here is the latest research.