title: Antiviral responses in mouse embryonic stem cells: differential development of cellular mechanisms in type I interferon production and response.
abstract: 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 (Wang, R., Wang, J., Paul, A. M., Acharya, D., Bai, F., Huang, F., and Guo, Y. L. (2013) J. Biol. Chem. 288, 15926-15936). Here, we report that mESCs are able to respond to type I IFNs, express IFN-stimulated genes, 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 IFN-stimulated genes and display weaker antiviral activity in response to type I IFNs when compared with 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.
authors: From the Departments of Biological Sciences and.
authors: Ruoxing
authors: R
authors: Wang
authors: From the Departments of Biological Sciences and.
authors: Jundi
authors: J
authors: Wang
authors: From the Departments of Biological Sciences and.
authors: Dhiraj
authors: D
authors: Acharya
authors: From the Departments of Biological Sciences and.
authors: Amber M
authors: AM
authors: Paul
authors: From the Departments of Biological Sciences and.
authors: Fengwei
authors: F
authors: Bai
authors: Chemistry and Biochemistry, University of Southern Mississippi, Hattiesburg, Mississippi 39406.
authors: Faqing
authors: F
authors: Huang
authors: From the Departments of Biological Sciences and yanlin.guo@usm.edu.
authors: Yan-Lin
authors: YL
authors: Guo
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D015153:Blotting, Western; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D002646:Chikungunya virus / Q000276:immunology / Q000502:physiology; D002522:Chlorocebus aethiops; D016207:Cytokines / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D053595:Embryonic Stem Cells / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D005347:Fibroblasts / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D054884:Host-Pathogen Interactions / Q000187:drug effects / Q000276:immunology; D007113:Immunity, Innate / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D007370:Interferon Type I / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D018062:La Crosse virus / Q000276:immunology / Q000502:physiology; D051379:Mice; D018613:Microscopy, Confocal; D053633:Receptor, Interferon alpha-beta / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014452:Ubiquitins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D014709:Vero Cells
chemical_list: D000998:Antiviral Agents; D016207:Cytokines; C489550:G1p2 protein, mouse; C508032:Ifnar1 protein, mouse; D007370:Interferon Type I; D014452:Ubiquitins; D053633:Receptor, Interferon alpha-beta
keywords: Antiviral Response; Double-stranded RNA (dsRNA); Embryonic Stem Cell; Innate Immunity; Interferon; Interferon-stimulated Genes; Viral Replication