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Cell. 2018 Jan 25;172(3):423-438.e25. doi: 10.1016/j.cell.2017.11.018. Epub 2017 Dec 14.

Intrinsic Immunity Shapes Viral Resistance of Stem Cells.

Author information

1
Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065, USA.
2
Laboratory of Membrane Biology, New York Blood Center, New York, NY 10065, USA; Department of Hematology, the First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan 450001, China.
3
Program in Immunogenomics, The Rockefeller University, New York, NY 10065, USA.
4
Laboratory of Membrane Biology, New York Blood Center, New York, NY 10065, USA; School of Life Sciences, Zhengzhou University, Zhengzhou, Henan 450001, China.
5
Department of Biology, New York University, New York, NY 10003, USA.
6
Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065, USA. Electronic address: ricec@rockefeller.edu.

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.

KEYWORDS:

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

PMID:
29249360
PMCID:
PMC5786493
DOI:
10.1016/j.cell.2017.11.018
[Indexed for MEDLINE]
Free PMC Article

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