MTOR signaling regulates Zika virus replication bidirectionally through autophagy and protein translation

Abstract

Zika virus (ZIKV) reemerged in 2016 and attracted much more attention worldwide. To date, the limited knowledge of ZIKV interactions with host cells in the early stages of infection impedes the prevention of viral epidemics and the treatment of ZIKV disease. The mammalian target of rapamycin (mTOR) signaling pathway plays an essential role in the regulation of autophagy and protein synthesis during multiple viral infections. This study aimed to investigate the functional role of mTOR signaling in ZIKV replication in human umbilical vein endothelial cells. Immunoblotting demonstrated that ZIKV infection inhibited mTORC1 signaling, enhancing autophagy but obstructing protein translation. Drugs or siRNA for interfering with mTOR signaling molecules were utilized to demonstrate that AKT/TSC2/mTORC1 signaling was involved in ZIKV infection and that autophagy promoted ZIKV production, but viral protein expression was regulated by mTORC1 signaling. Moreover, confocal microscopy indicated a robust correlation between autophagy and viral RNA transcription. This study clarifies the dual functions of mTOR signaling during ZIKV infection and provides theoretical support for developing potential anti-ZIKV drugs based on mTOR signaling molecules and deeper insights to better understand the mechanism between ZIKV and host cells.