Developmental Biology - Stem Cells|
How Stem Cells Self Protect From Viruses
An immune system discovery could help development of stem cell therapies...
New research discovers how stem cells are protected from viruses and could improve development of stem cell therapies in medicine. These finding could boost the immune response of stem cells — which are early stage cells without specialized function — to be used in treating diseases or repairing damaged tissues.
The research has identified ways to switch on the interferon response — a key part of the immune system that protects against viruses in stem cells.
University of Edinburgh, Scotland, researchers studied mouse embryo stem cells to understand how they develop resistance to viruses, before those cells become specialized.
The research team has discovered a protein - mitochondrial antiviral signalling protein (MAVS) - switches on an immune response in stem cells.
• A small molecule - miR-673 - regulates when MAVS protein is turned on and off.
• When miR-673 is removed in the lab from stem cells, production of MAVS protein is restored, switching on an anti-viral response.
Although an antiviral response may be absent from embryonic stem cells as it might disrupt development, researchers believe the same mechanism likely operates in all other human stem cells.
Researchers hope their findings will make use of stem cells more efficient, to one day be given to patients to replace cells lost or damaged by degenerative diseases such as Parkinson's or diabetes. The study, published in eLife, was funded by the Wellcome Trust.
"Unveiling how this crucial antiviral mechanism is switched off and methods to switch it back on in a controlled manner, could make stem cell therapies much more efficient."
Jeroen Witteveldt PhD, School of Biological Sciences, University of Edinburgh, Scotland.
When mammalian cells detect a viral infection, they initiate a type I Interferon (IFNs) response as part of their innate immune system. This antiviral mechanism is conserved in virtually all cell types, except for embryonic stem cells (ESCs) and oocytes which are intrinsically incapable of producing IFNs. Despite the importance of the IFN response to fight viral infections, the mechanisms regulating this pathway during pluripotency are still unknown. Here we show that, in the absence of miRNAs, ESCs acquire an active IFN response. Proteomic analysis identified MAVS, a central component of the IFN pathway, to be actively silenced by miRNAs and responsible for suppressing IFN expression in ESCs. Furthermore, we show that knocking out a single miRNA, miR-673, restores the antiviral response in ESCs through MAVS regulation. Our findings suggest that the interaction between miR-673 and MAVS acts as a switch to suppress the antiviral IFN during pluripotency and present genetic approaches to enhance their antiviral immunity.
Jeroen Witteveldt, Lisanne I Knol, Sara Macias.
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Researchers discover how stem cells are protected from viral infection. Boosting the immune response of stem cells could be usefulin treating diseases or repairing damaged tissue. Credit: Public Domain