Enteroviruses, including subtype EV-A71, infect the brain, liver, heart, and other organs, causing a myriad of human diseases. This spectrum of disease is thought to be due, in part, to differential binding to host cells, and additional knowledge of enterovirus cell entry is essential for therapeutic development. In this issue of the JCI, Yeung et al. provide evidence of a novel EV-A71 entry factor, a host-produced tryptophan tRNA synthetase (hWARS), that facilitates entry of multiple subtypes of enteroviruses. hWARS is a cytoplasmic enzyme that is essential for translation but also upregulated and secreted during inflammatory processes. The results of this study support the notion of secreted hWARS as an unconventional virus entry factor that raises interesting questions about mechanisms by which inflammation and a tRNA synthetase facilitate viral pathogenesis.