Title | Intrinsic Immunity Shapes Viral Resistance of Stem Cells. |
Publication Type | Journal Article |
Year of Publication | 2018 |
Authors | Wu X, Thi VLoan Dao, Huang Y, Billerbeck E, Saha D, Hoffmann H-H, Wang Y, Silva LAVale, Sarbanes S, Sun T, Andrus L, Yu Y, Quirk C, Li M, MacDonald MR, Schneider WM, An X, Rosenberg BR, Rice CM |
Journal | Cell |
Volume | 172 |
Issue | 3 |
Pagination | 423-438.e25 |
Date Published | 2018 01 25 |
ISSN | 1097-4172 |
Keywords | Animals, Cells, Cultured, Female, HEK293 Cells, Humans, Immunity, Innate, Interferons, Male, Mice, Mice, Inbred NOD, Pluripotent Stem Cells, Species Specificity, Virus Diseases |
Abstract | Stem cells are highly resistant to viral infection compared to their differentiated progeny; however, the mechanism is mysterious. Here, we analyzed gene expression in mammalian stem cells and cells at various stages of differentiation. We find that, conserved across species, stem cells express a subset of genes previously classified as interferon (IFN) stimulated genes (ISGs) but that expression is intrinsic, as stem cells are refractory to interferon. This intrinsic ISG expression varies in a cell-type-specific manner, and many ISGs decrease upon differentiation, at which time cells become IFN responsive, allowing induction of a broad spectrum of ISGs by IFN signaling. Importantly, we show that intrinsically expressed ISGs protect stem cells against viral infection. We demonstrate the in vivo importance of intrinsic ISG expression for protecting stem cells and their differentiation potential during viral infection. These findings have intriguing implications for understanding stem cell biology and the evolution of pathogen resistance. |
DOI | 10.1016/j.cell.2017.11.018 |
Alternate Journal | Cell |
PubMed ID | 29249360 |
PubMed Central ID | PMC5786493 |
Grant List | DP5 OD012142 / OD / NIH HHS / United States R01 AI091707 / AI / NIAID NIH HHS / United States R01 DK100810 / DK / NIDDK NIH HHS / United States U19 AI111825 / AI / NIAID NIH HHS / United States |
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