After detecting some strains of the flu virus, human body cells keep the disease from spreading by making the ultimate sacrifice: They kill themselves through programmed cell death.
Scientists have identified the protein that triggers this means of self-defense against the flu and say it could be used to ease symptoms of the disease or to control a potential pandemic.
In new research published Oct. 12 in Cell Host & Microbe, scientists found how cells recognize the influenza A virus and cause self-programmed cell death. The study is the result of a collaboration between researchers at UT-Austin, Fox Chase Cancer Center, Icahn School of Medicine and St. Jude Children’s Research Hospital.
Influenza, also known as the flu, is an infectious viral disease that affects millions of people each year, according to the World Health Organization. Infected people exhibit symptoms such as fever, sore throat, cough and runny nose. Coughing spreads the virus into the air, where other people can breathe it in.
Although most people recover from seasonal flu within a week, elderly people, or those with weakened immune systems, can die from the infection. Pandemic strains such as the Spanish flu have the potential to be more deadly.
The influenza A strain infects and reproduces inside cells on the top layer of the upper respiratory tract. To prevent the virus from multiplying, infected cells can activate two different death pathways called apoptosis and necroptosis.
“This was thought to represent a host immune mechanism, like a defense strategy, to eliminate infected cells,” said Siddharth Balachandran, associate professor at Fox Chase Cancer Center and co-author of the study. “It’s an altruistic strategy of immunity.”
Researchers knew about this defense mechanism, but how exactly cells recognized the virus and prompted cell death was poorly understood.
The team of scientists found that a protein named DNA-dependent Activator of Interferon, or DAI, is activated in the presence of the influenza A virus and triggers the two cell death pathways. In the study, mice lacking DAI did not elicit cell death and were unable to control replication of the virus.
Jason Upton, UT assistant professor of molecular genetics and microbiology and co-author of the study, said these death pathways are crucial host defense mechanisms.
“Animals that lack DAI don’t have the ability to trigger necroptosis in response to influenza and often succumb to the infection,” Upton said.
Researchers were surprised to find that DAI, a DNA sensor, was able detect the influenza virus, which is composed of RNA. DAI has been found to play a role in immune response to DNA viruses, such as herpesvirus. More research is needed to better understand this mechanism, Upton said.
The discovery has potential future applications in treating and alleviating flu symptoms, Balachandran said. If a pandemic influenza strain were to hit, doctors could potentially use therapies which utilize these cell death pathways.
“We’ve got circulating strains of influenza with pandemic potential — avian flu, for example,” Balachandran said. “We can activate this death pathway in the cases of these virulent strains of influenza.”