Article: From infection-dodging stem cells, new tactics for research on viral disease

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For a stem cell, the future is wide open. It can divide infinitely to create more stem cells, or it can grow up into other kinds of cells, taking its place in the heart, brain, or other organs. But the stem cell loses something during that maturation: its remarkable ability to fight off viruses.

It's important that stem cells be protected from infection: some of them are starting material for babies, and others make up a crucial reservoir to build or rebuild body tissues as needed. An intruder that damaged or killed stem cells would be disastrous, but how they go about protecting themselves has been a decades-long mystery. In a recent study in Cell, Rockefeller scientists offer up an explanation: stem cells are on constant high alert, bristling with preemptive defenses—means of protection that other cells use only when a virus actually attacks.

"That just makes sense," says senior author Charlie M. Rice, the Maurice R. And Corinne P. Greenberg Professor in Virology at The Rockefeller University. "Because stem cells are pretty important, the body would want to be especially protective of them."

And for the past 40 years, scientists have been puzzled by another funny thing about stem cells: they're unusually resistant to viral attack. Recent experiments by Rice's group and others focused on plagues including dengue, HIV, and Zika: stem cells rebuff them all.

Xianfang Wu, a postdoctoral researcher in Rice's lab, was working with stem cells to make liver cells and study hepatitis infections when he serendipitously found a clue: stem cells and liver cells use different viral defenses.

I have yet to read the paper but at first glance this sounds like a really neat piece of research - an interesting serendipitous discovery, thoroughly followed up.

https://phys.org/news/2018-03-infection-dodging-stem-cells-tactics-viral.amp

Full paper: Xianfang Wu et al. Intrinsic Immunity Shapes Viral Resistance of Stem Cells, Cell(2017). DOI: 10.1016/j.cell.2017.11.018

Highlights

• •Pluri-/multipotent stem cells exhibit intrinsic expression of ISGs
• •Different stem cells express cell-type-specific groups of ISGs
• •Intrinsically expressed ISGs mediate antiviral resistance ex vivo and in vivo
• •Dynamic expression of ISGs is conserved across species

Summary
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.