‘Double-edged’ transcription factor affects flu response

A genetic transcription factor involved in lung cancer and pneumonia also mediates the body’s response to influenza, according to a new paper from University of Illinois Chicago scientists. The discovery could lead to strategies to boost the immune system to fight viruses, according to researcher Jing Liu.

Transcription factors are proteins that turn genes on and off, controlling cellular functions such as growth and defense against infection. Liu’s laboratory studies a transcription factor called Miz1. It’s linked to lung injury and inflammation, which can occur when the immune system response is overactive. Previous work on bacterial infections found that too much Miz1 suppresses disease-fighting immune factors; too little, and the infection is cleared, but with a risk of inflammation. 

“Inflammation is a double-edged sword,” said Liu, associate professor of surgery in the College of Medicine. “If you increase the immune response, it helps to fight the infection. But if inflammation causes immunopathology, that can override the beneficial effect.” 

In the Science Signaling paper, Liu’s group found that the same relationship exists for viral infection with influenza A. After infection, lung cells accumulated Miz1, which decreased the production of disease-fighting factors called interferons. This served as evidence that viruses boost Miz1 to hide from the immune system.

Deactivating Miz1 led to higher interferon production and improved viral clearance in cells and in mice. The researchers also determined the cellular pathways that repress or activate Miz1, providing potential targets for new antiviral therapies.

“This is a very promising alternative strategy to fight virus-induced pneumonia,” Liu said. Instead of attacking the virus directly with medication, “we can boost the host immune system against the virus.” 

Liu, who is a member of the University of Illinois Cancer Center, also has studied the role of Miz1 in lung cancer, where tumors show elevated levels of the transcription factor.

“In lung cancer, Miz1 can promote tumor cell proliferation. Without Miz1, tumor cells undergo cell death,” Liu said. “Host cells are very smart to use conserved signaling pathways to combat different insults, but it also can leave them vulnerable to exploitation.”