Stem cells are the precursors of all the specialized cells in our body, as they can develop into many different cell types. These unspecialized cells play a vital role in maintaining the architecture, integrity, and renewal of our body’s tissues. Just like any other cell, stem cells are susceptible to infection by RNA viruses such as SARS-CoV-2 and Zika virus. Upon infection, these and other viruses will enter the host cell to replicate. For most specialized cells in mammals, the first line of defense against this viral infection uses proteins called interferons. However, since stem cells lack this interferon response, it was previously unknown how they protect themselves from viral infection.
Researchers at the Francis Crick Institute have recently discovered the mechanism by which stem cells fend off viral invaders. Analysis of mouse stem cells revealed a shorter version of a previously known protein Dicer, which the scientists named antiviral Dicer (aviD). AviD has better antiviral properties compared to Dicer. AviD fights viruses through a process called RNA interference, whereby it generates small RNAs that target and cleave replicating viral genes. Human cells that were genetically engineered to contain aviD were infected with three times fewer the amount of SARS-CoV-2 viral particles than those cells that lacked aviD. The researchers also grew miniature mouse brain organoids and infected them with either SARS-CoV-2 or Zika virus, and the organoids containing aviD grew more quickly and produced less viral material than the organoids lacking this protein. Notably, once stem cells finish developing into their specialized cell types, production of aviD is lost.
Interestingly, this antiviral mechanism by RNA interference is the same one that is used by plants and invertebrates and was previously thought to have disappeared as mammals evolved. While mammalian cells possess the ability to use this process, it is only relied upon by stem cells, perhaps to prevent any damage that might occur from the interferon response. The researchers plan on continuing their studies to further understand how these cells are protected from viruses. These findings could one day be exploited for use in antiviral therapies, as RNA interference strategies may be useful against RNA viruses such as Zika virus and SARS-CoV-2.
Dr. Caetano Reis e Sousa is currently an Assistant Research Director and Senior Group Leader of the Immunobiology Laboratory at the Francis Crick Institute. Dr. Enzo Poirier is a post-doctoral fellow at the Francis Crick Institute.
Managing Correspondent: Lauren Davancaze
Press Articles: “Stem cells can use same method as plants and insects to protect against viruses,” Phys.org
Original Journal Article: “An isoform of Dicer protects mammalian stem cells against multiple RNA viruses,” Science
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