New findings show mouse stem cells react just like plants and invertebrates to viruses, granting potential therapeutic insights in the lab.
Scientists at the Francis Crick Institute have found a mechanism in mouse stem cells that was previously thought to have disappeared as mammals evolved.
When a host is infected by a disease such as Covid-19 or Zika, a virus enters the cell to replicate. In the differentiated cells of mammals, proteins called interferons are produced to fight off this invader.
Stem cells, however, can’t trigger an interferon response, which has led to uncertainty about how they protect themselves.
Strangely, invertebrates and plants may offer insight into how these stem cells survive.
These forms of life work a little differently. Using a process called RNA interference, they produce an antiviral Dicer (aviD) that cuts up viral RNA and stops the virus from replicating.
In a study published on 8 July in Science, researchers have found that while mouse stem cells can’t produce interferons, they can produce aviD.
“It’s fascinating to learn how stem cells protect themselves against RNA viruses. The fact this protection is also what plants and invertebrates use suggests it might be something that goes far back in mammalian history, right up to when the evolutionary tree spilt,” said Caetano Reis e Sousa, an author on the paper and group leader of the immunobiology laboratory at the Francis Crick Institute.
“By learning more about this process, and uncovering the secrets of our immune system we are hoping to open up new possibilities for drug development as we strive to harness our body’s natural ability to fight infection.”
In laboratory experiments which exposed engineered human cells to SARS-CoV-2, the virus infected three times fewer stem cells when aviD was present in the cells compared to when the researchers removed this protein.
The scientists also grew mini brain organoids from mouse embryonic stem cells and found that, when infected with Zika virus, the organoids with aviD grew more quickly and less viral material was produced than in organoids without this protein.
Similarly, when organoids were infected with SARS-CoV-2, there were fewer infected stem cells in the organoids with aviD.
Enzo Poirier, co-author and postdoc in the Immunobiology Laboratory at the Francis Crick Institute, said: “Why stem cells use this different mechanism of defence remains a mystery.
“It might be that the interferon process would cause too much harm to stem cells, so mammals, including humans, have evolved to shield these precious cells from this damage. There is still a lot of uncertainty about how these cells are protected from viruses, which we’re excited to explore further.”