Zika virus induces massive cytoplasmic vacuolization and paraptosis-like death in infected cells

We report that ZIKV induces massive vacuolization followed by "implosive" cell death in human epithelial cells, primary skin fibroblasts and astrocytes, a phenomenon which is exacerbated when IFITM3 levels are low. It is reminiscent of paraptosis, a caspase-independent, non-apoptotic form of cell death associated with the formation of large cytoplasmic vacuoles. We further show that ZIKV-induced vacuoles are derived from the endoplasmic reticulum (ER) and dependent on the PI3K/Akt signaling axis. Inhibiting the Sec61 ER translocon in ZIKV-infected cells blocked vacuole formation and viral production. Our results provide mechanistic insight behind the ZIKV-induced cytopathic effect and indicate that IFITM3, by acting as a gatekeeper for incoming virus, restricts virus takeover of the ER and subsequent cell death.

Source: EMBO Journal - June 14, 2017 Category: Molecular Biology Authors: Monel, B., Compton, A. A., Bruel, T., Amraoui, S., Burlaud-Gaillard, J., Roy, N., Guivel-Benhassine, F., Porrot, F., Genin, P., Meertens, L., Sinigaglia, L., Jouvenet, N., Weil, R., Casartelli, N., Demangel, C., Simon-Loriere, E., Moris, A., Roingeard, P. Tags: Microbiology, Virology & Host Pathogen Interaction Articles Source Type: research