When mammalian cells detect a viral infection, they initiate a type I Interferon (IFNs) response as part of their innate immune system. This antiviral mechanism is conserved in virtually all cell types, except for embryonic stem cells (ESCs) and oocytes which are intrinsically incapable of producing IFNs. Despite the importance of the IFN response to fight viral infections, the mechanisms regulating this pathway during pluripotency are still unknown. Here we show that, in the absence of miRNAs, ESCs acquire an active IFN response. Proteomic analysis identified MAVS, a central component of the IFN pathway, to be actively silenced by miRNAs and responsible for suppressing IFN expression in ESCs. Furthermore, we show that knocking out a single miRNA, miR-673, restores the antiviral response in ESCs through MAVS regulation. Our findings suggest that the interaction between miR-673 and MAVS acts as a switch to suppress the antiviral IFN during pluripotency and present genetic approaches to enhance their antiviral immunity.
All data generated or analysed during this study are included in the manuscript and supporting files. Source data files for Figure 3B are included in the Supplementary Excel File
- Sara Macias
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
- Xuetao Cao, Zhejiang University School of Medicine, China
© 2019, Witteveldt et al.
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