How influenza virus hijacks cell machines to suppress immune alarm signals

Researchers at the University of Gothenburg said influenza viruses manipulate the body’s gene regulatory systems to accelerate its own spread. Their research also shows that already approved drugs may help to enhance immune defenses, but their effectiveness in humans has not yet been confirmed.

Published in the journal Nucleic Acids Research, the study concerns previously unknown strategies that the influenza A virus used to take over the body’s systems. This study shows that viruses typically regulate which genes are active in cells and manipulate proteins that help transform this protein into the immune system.

A protein called Aga2 is involved in what is known as RNA interference, a mechanism that regulates gene activity. ago2 normally works outside the cell nucleus in connection with infection, but the virus moves proteins to the nucleus and turns off key genes in the immune system.

Virus mutes alarm

This is primarily related to type I interferons. This is a signaling substance that infected cells use to warn their neighbors and enhance the body’s defenses.

“The most surprising thing is that the virus hijacks such a basic, well-regulated system as RNA interference, and it uses it if it is not using it in the nucleus,” said Aish Sarshad, an associate professor of cell and molecular biology at the Sargrenska Academy at the University of Gothenburg and one of the senior authors of the study.

Much of the laboratories was carried out by Hsiang-chi Huang, a postdoctoral member of the group at the time. Studies show that Aga2 proteins are bound to genes that chase the tumor suppressor p53 into the nucleus, regulating body alarm signals and turning them off.

New antiviral treatments

Researchers also investigated whether the virus could halt its manipulation. To this end, they used arsenic arsenic trioxide (ATO), a drug approved for the treatment of blood cancer types. In both cell cultures and mice, this drug was shown to increase interferon production and reduce the amount of virus in the lungs.

This finding indicates that it may be possible to affect the body’s RNAi system and slow viral infections. This slows down not only the flu, but perhaps even other RNA viruses.

“Now we want to continue our research to see if the same mechanism is seen in other types of infections, paving the way for an entirely new type of antiviral therapy that targets not just the virus but how it uses its own cells,” says Sarshad.