Intrinsic Immunity Shapes Viral Resistance of Stem Cells

Xianfang Wu, Viet Loan Dao Thi, Yumin Huang, Eva Billerbeck, Debjani Saha, Hans Heinrich Hoffmann, Yaomei Wang, Luis A.Vale Silva, Stephanie Sarbanes, Tony Sun, Linda Andrus, Yingpu Yu, Corrine Quirk, Melody Li, Margaret R. MacDonald, William M. Schneider, Xiuli An, Brad R. Rosenberg, Charles M. Rice

Research output: Contribution to journalArticle

65 Scopus citations

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. Intrinsic expression of interferon-stimulated genes makes stem cells resistant to infections, preserving their pool throughout the organism's lifespan.

Original languageEnglish (US)
Pages (from-to)423-438.e25
JournalCell
Volume172
Issue number3
DOIs
StatePublished - Jan 25 2018
Externally publishedYes

Keywords

  • antiviral mechanisms
  • interferon-stimulated genes
  • intrinsic immunity
  • stem cell differentiation
  • tissue stem cells
  • tissue tropism
  • viral infection

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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  • Cite this

    Wu, X., Dao Thi, V. L., Huang, Y., Billerbeck, E., Saha, D., Hoffmann, H. H., Wang, Y., Silva, L. A. V., Sarbanes, S., Sun, T., Andrus, L., Yu, Y., Quirk, C., Li, M., MacDonald, M. R., Schneider, W. M., An, X., Rosenberg, B. R., & Rice, C. M. (2018). Intrinsic Immunity Shapes Viral Resistance of Stem Cells. Cell, 172(3), 423-438.e25. https://doi.org/10.1016/j.cell.2017.11.018