Ancient antiviral mechanism hidden in mammalian cells but still active

04 November 2016

Flu virus

Image: Flu virus

Francis Crick Institute scientists have revealed a new way that mammalian cells can attack viruses - using a method that was previously only thought to be used by invertebrates (less complex animals without backbones).

However this ancient system of fighting viruses is masked by another system that has developed specifically in mammals - called the interferon system.

The research gives insights into the evolution of our immune system. It also leads the way for research into new ways to exploit this mechanism in the fight against human viruses.

Pierre Maillard, in Caetano Reis e Sousa's research group, at the Crick led the work. He explains: "Plants, insects and nematode worms fight back against virus infections using a mechanism called RNA interference.

"Many viruses contain RNA molecules as their genetic material and when they infect a host cell these get copied into double stranded RNA.

"During RNA interference, double stranded RNA molecules are chopped up into small pieces that are then bound to a protein complex, which is instructed to cut up any RNA molecules in the cell that are complementary to the small RNA fragments. This means that the viral RNA genome itself is effectively destroyed."

To monitor and trace the activity of antiviral RNA interference, the researchers engineered cells in which the interferon system didn't work. They introduced synthetic molecules of double stranded RNA into these cells as a proxy for viral infection and used fluorescent markers  that allowed them to detect every cell that incorporated the double stranded RNA.

The researchers saw a decrease in the level of fluorescent protein - indicating that RNA interference was indeed active. The results further indicated that RNA interference can be boosted by pre-stimulation with double stranded RNA molecules in order to vaccinate the cells against invading viruses containing complementary sequences.

Professor Reis e Sousa says: "Our study reveals another set of weapons that mammalian cells have at their disposal to attack viruses. It opens up new avenues of research aimed at understanding the cell types and contexts in which this ancestral mechanism plays a role in antiviral defence.

"While our study provides some new insights into the evolution of our immune system, it may also offer new possibilities to exploit these defences to fight against virus infection, a threat that the human population is constantly facing."

The paper, Inactivation of the type I interferon pathway reveals long double stranded RNA-mediated RNA interference in mammalian cells, is published in the EMBO Journal.

  • Scientists have discovered that an ancient system used by invertebrates to fight viruses still exists in mammals, but is masked by a mammalian-specific antiviral mechanism.
  • The work offers insights into the evolution of our immune system and might lead to new ways to fight human viruses.