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.