THANKS TO a spot of clever angling, scientists at Trinity College Dublin have fished out a key step in how our cells detect invading viruses.
Their approach baited a protein in our cells that acts as a "sensor" for the presence of virus DNA and helps trigger a response to shut the cell down and stop the infection spreading.
"For a long time people have known that when viruses infect cells, the cells are able to mount an anti-viral response," explained Prof Andrew Bowie, an author on the paper published online in Nature Immunology.
"But how these anti-viral responses are triggered has only really been discovered in the past 10 years, and the real detail on the mechanisms the cells use are only becoming apparent," he said. The search has been hotting up recently for virus sensors in a compartment of the cell called the cytosol, according to Prof Bowie, an associate professor at Trinity's School of Biochemistry and Immunology.
"For the last four or five years people have been searching quite frantically for these sensors and very few of them have been discovered," he said. But the Trinity group managed to hook their prey by chopping up segments of DNA from viruses, including a pox virus called Vaccinia, and casting them into immune cells called macrophages in the lab.
Several proteins took the bait and bound to the viral DNA, allowing the scientists to reel them in and analyse them.
"There were lots of [ attached] proteins and we had to decide which was the most important," said Prof Bowie. "So we tested a number of proteins on the list to see which ones were increased during a virus infection; that's often a signal that they are the really important ones."
That led them to a protein called IFI16, which Prof Bowie described as "a surprise" because that protein was not well known for being out in that part of the cell. The study, which was funded by Science Foundation Ireland, also found that IFI16 stuck to segments of DNA from herpes simplex virus, and if the researchers experimentally reduced IFI16 in various types of cells, it impaired the ability of those cells to respond to viruses, said Prof Bowie.
More generally, IFI16 may be an important component of how the immune system responds to any DNA that is added to cells, perhaps from bacteria, or even our own genetic material in the case of auto-immune disease, he added.
The research also involved TCD scientists Dr Leonie Unterholzner, Dr Sinéad Keating and Marcin Baran and collaborations with the University of Massachusetts Medical School, the University of Aarhus, Denmark and the National Institutes of Health, Maryland.