The influenza virus manipulates the body’s gene regulation system to accelerate its own spread, according to researchers at the University of Gothenburg. Their study also shows that an already approved drug could help strengthen immune defenses—though its effect in humans remains to be confirmed.
The study, published in the journal Nucleic Acids Research, concerns a previously unknown strategy used by the influenza A virus to take over the body's own systems. The study shows that the virus manipulates a protein that normally helps regulate which genes should be active in the cell, turning this protein against the immune system.
The protein, referred to as AGO2, is involved in what is known as RNA interference, a mechanism that regulates gene activity. While AGO2 usually works outside the cell nucleus, in conjunction with infection, the virus manages to move the protein into the nucleus, where it turns off genes that are key to the immune system.
This primarily concerns type I interferons – signaling substances used by infected cells to warn their neighbors and strengthen the body's defenses.
Aishe Sarshad, associate professor of cellular and molecular biology at Sahlgrenska Academy at the University of Gothenburg, is one of the study's senior authors:
"Most surprising was that the virus manages to hijack such a fundamental and well-regulated system as RNA interference – even using it inside the nucleus, where it isn't normally found," says Aishe Sarshad.
Much of the laboratory work was performed by Hsiang-Chi Huang, a postdoc member of the group at the time. The work shows that the AGO2 protein follows the tumor suppressor p53 into the nucleus, binding itself to genes that regulate the body's alarm signals and turning them off.
The researchers also investigated whether the manipulative actions of the virus could be stopped. To this end, they used arsenic trioxide (ATO), a drug approved for treating a type of blood cancer. In both cell cultures and mice, the drug was shown to increase the production of interferons and reduce the amount of virus in the lungs.
This discovery indicates that it may be possible to influence the body's own RNAi system to slow viral infections – and not just influenza, but perhaps even other RNA viruses.
"Now, we want to continue our investigations to see whether the same mechanism is found in other types of infections. This paves the way for a completely new type of antiviral treatment, where we target not only the virus, but also how it uses our own cells," says Aishe Sarshad.