Document Type

Article

Publication Date

5-31-2013

Department

Biological Sciences

Abstract

Embryonic stem cells (ESCs) are considered to be a promising cell source for regenerative medicine because of their unlimited capacity for self-renewal and differentiation. However, little is known about the innate immunity in ESCs and ESC-derived cells. We investigated the responses of mESCs to three types of live viruses; La Crosse virus (LACV), West Nile virus (WNV), and Sendai virus (SeV). Our results demonstrated mESCs were susceptible to viral infection, but they were unable to express type I interferons (IFNα and IFNβ,IFNα/β which differ from fibroblasts (10T1/2 cells) that robustly express IFNα/β upon viral infections. The failure of mESCs to express IFNα/β was further demonstrated by treatment with polyIC (polyinosinic-polycytidylic), a synthetic viral dsRNA analog that strongly induced IFNα/β in 10T1/2 cells. Although polyIC transiently inhibited the transcription of pluripotency markers, the stem cell morphology was not significantly affected. However, polyIC can induce dsRNA-activated protein kinase (PKR) in mESCs and this activation resulted in a strong inhibition of cell proliferation. We conclude that the cytosolic receptor PKR is functional, but the mechanisms that mediate type I IFN expression are deficient in mESCs. This conclusion is further supported by the findings that the major viral RNA receptors are either expressed at very low levels (TLR3 and MDA5) or may not be active (RIG-I) in mESCs.

Publication Title

Journal of Biological Chemistry

Volume

288

Issue

22

First Page

15926

Last Page

15936

mouse embryonic stem cells.pdf (37 kB)
Supplementary Table 1. Primer Sequences for RT-qPCR

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