title: Mouse embryonic stem cells are deficient in type I interferon expression in response to viral infections and double-stranded RNA.
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 mouse (m)ESCs to three types of live viruses as follows: La Crosse virus, West Nile virus, and Sendai virus. 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, 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 in mESCs, and this activation resulted in a strong inhibition of cell proliferation. We conclude that the cytosolic receptor dsRNA-activated protein kinase 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 (retinoic acid-inducible gene I) in mESCs.
authors.affiliation: Department of Biological Sciences, University of Southern Mississippi, Hattiesburg, Mississippi 39406, USA.
authors.forename: Ruoxing
authors.initials: R
authors.lastname: Wang
authors.forename: Jundi
authors.initials: J
authors.lastname: Wang
authors.forename: Amber M
authors.initials: AM
authors.lastname: Paul
authors.forename: Dhiraj
authors.initials: D
authors.lastname: Acharya
authors.forename: Fengwei
authors.initials: F
authors.lastname: Bai
authors.forename: Faqing
authors.initials: F
authors.lastname: Huang
authors.forename: Yan-Lin
authors.initials: YL
authors.lastname: Guo
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000096:biosynthesis / Q000276:immunology; D053487:DEAD-box RNA Helicases / Q000096:biosynthesis / Q000276:immunology; D053595:Embryonic Stem Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism* / Q000821:virology; D006801:Humans; D007369:Interferon Inducers / Q000494:pharmacology; D000072640:Interferon-Induced Helicase, IFIH1; D016898:Interferon-alpha / Q000096:biosynthesis* / Q000276:immunology; D016899:Interferon-beta / Q000096:biosynthesis* / Q000276:immunology; D051379:Mice; D039904:Pluripotent Stem Cells / Q000276:immunology / Q000378:metabolism* / Q000821:virology; D011070:Poly I-C / Q000494:pharmacology; D012327:RNA Virus Infections / Q000276:immunology / Q000378:metabolism*; D012328:RNA Viruses / Q000276:immunology / Q000378:metabolism*; D012330:RNA, Double-Stranded / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D012367:RNA, Viral / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D051196:Toll-Like Receptor 3 / Q000096:biosynthesis / Q000276:immunology; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D000943:Antigens, Differentiation; D007369:Interferon Inducers; D016898:Interferon-alpha; D012330:RNA, Double-Stranded; D012367:RNA, Viral; C519703:TLR3 protein, mouse; D051196:Toll-Like Receptor 3; D016899:Interferon-beta; C510592:Ifih1 protein, mouse; D053487:DEAD-box RNA Helicases; D000072640:Interferon-Induced Helicase, IFIH1; D011070:Poly I-C
keywords: Double-stranded RNA; Embryonic Stem Cell; Innate Immunity; Interferon; Protein Kinase RNA (PKR); Toll-like Receptors (TLR)