Antiviral Responses in Mouse Embryonic Stem Cells: Differential Development of Cellular Mechanisms in Type I Interferon Production and Response [Cell Biology]

June 25th, 2014 by Wang, R., Wang, J., Acharya, D., Paul, A. M., Bai, F., Huang, F., Guo, Y.-L.

We have recently reported that mouse embryonic stem cells (mESCs) are deficient in expressing type-I interferons (IFNs) in response to viral infection and synthetic viral RNA analogs (J. Biol. Chem. 2013, 288: 15926-15936). Here, we report that mESCs are able to respond to type-I IFNs, express IFN-stimulated genes (ISGs), and mediate the antiviral effect of type-I IFNs? against La Crosse virus and chikungunya virus. The major signaling components in the IFN pathway are expressed in mESCs. Therefore, the basic molecular mechanisms that mediate the effects of type-I IFNs are functional in mESCs, however, these mechanisms may not yet be fully developed as mESCs express lower levels of ISGs and display weaker antiviral activity in response to type-I IFNs when compared to fibroblasts. Further analysis demonstrated that type-I IFNs do not affect the stem cell state of mESCs. We conclude that mESCs are deficient in type-I IFN expression, but they can respond to and mediate the cellular effects of type-I IFNs. These findings represent unique and uncharacterized properties of mESCs and are important for understanding innate immunity development and ESC physiology.
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