%0 Journal Article
%T Human tryptophanyl-tRNA synthetase is an IFN-污每inducible entry factor for Enterovirus
%A Anna J. Zhang
%A Chaoyu Zhang
%A Cyril C. Y. Yip
%A Dong-Yan Jin
%A Jade L. L. Teng
%A Janice Y. C. Lo
%A Jasper F. W. Chan
%A Jian-Piao Cai
%A Kin-Hang Kok
%A Kwok-Hung Chan
%A Kwok-Yung Yuen
%A Lilong Jia
%A Man Lung Yeung
%A Patrick C. Y. Woo
%A Shin-Ru Shih
%A Susanna K. P. Lau
%A Wan-Man Wong
%J The Journal of Clinical Investigation
%D 2018
%R 10.1172/JCI99411
%X Enterovirus A71 (EV-A71) receptors that have been identified to date cannot fully explain the pathogenesis of EV-A71, which is an important global cause of hand, foot, and mouth disease and life-threatening encephalitis. We identified an IFN-污每inducible EV-A71 cellular entry factor, human tryptophanyl-tRNA synthetase (hWARS), using genome-wide RNAi library screening. The importance of hWARS in mediating virus entry and infectivity was confirmed by virus attachment, in vitro pulldown, antibody/antigen blocking, and CRISPR/Cas9-mediated deletion. Hyperexpression and plasma membrane translocation of hWARS were observed in IFN-污每treated semipermissive (human neuronal NT2) and cDNA-transfected nonpermissive (mouse fibroblast L929) cells, resulting in their sensitization to EV-A71 infection. Our hWARS-transduced mouse infection model showed pathological changes similar to those seen in patients with severe EV-A71 infection. Expression of hWARS is also required for productive infection by other human enteroviruses, including the clinically important coxsackievirus A16 (CV-A16) and EV-D68. This is the first report to our knowledge on the discovery of an entry factor, hWARS, that can be induced by IFN-污 for EV-A71 infection. Given that we detected high levels of IFN-污 in patients with severe EV-A71 infection, our findings extend the knowledge of the pathogenicity of EV-A71 in relation to entry factor expression upon IFN-污 stimulation and the therapeutic options for treating severe EV-A71每associated complications
%U https://www.jci.org/articles/view/99411