ABSTRACT
The cellular fate after infection with human coronaviruses (HCoVs) is typically death. Previous data suggest, however, that the transcriptional state of an individual cell may sometimes allow additional outcomes of infection. Here, to probe the range of interactions a permissive cell type can have with a HCoV, we perform a CRISPR activation screen with HCoV-229E. The screen identified the transcription factor ZBTB7A, which strongly promotes cell survival after infection. Rather than suppressing viral infection, ZBTB7A upregulation allows the virus to induce a persistent infection and homeostatic state with the cell. We also find that control of oxidative stress is a primary driver of cellular survival during HCoV-229E infection. These data illustrate that, in addition to the nature of the infecting virus and the type of cell that it encounters, the basal gene expression profile of cell prior to infection can affect the eventual cellular fate. Graphical The fates of infected cells can affect viral pathogenesis. Zhu et al. show that the upregulation of ZBTB7A can convert a cytolytic human coronavirus infection to a persistent, homeostatic one. Continued work in this area may ultimately explain the divergence of clinical presentations associated with respiratory viral infections.