Fox Chase Researchers Discover Key Immune Mechanism That Fights Influenza by Destroying Infected Cells

Siddharth Balachandran, PhD
Siddharth Balachandran, PhD

PHILADELPHIA (October 13, 2016) – In a laboratory finding, Fox Chase Cancer Center researchers have identified a cellular protein that senses the presence of influenza virus and rapidly destroys the infected cell.

“This sensor, a protein called DAI, recognizes viral RNA and sets off a powerful auto-destruct program so that the infected cell doesn’t become a virus factory,” said Siddharth Balachandran, PhD, lead author of the study, published in the journal Cell Host & Microbe on Oct. 13. “Without this protein, the influenza-infected cell is unable to kill itself, and continues to produce high levels of progeny virus particles. These newly-minted viruses then rampage through the lung, severely compromising lung function, and ultimately killing the host.”

“The DAI-based influenza sensing mechanism is your body’s early immune response to being infected,” he said. “The infected cells selflessly kill themselves so that virus spread is curbed and the body has time to kick into gear other immune mechanisms that then eradicate the virus from the infected lung.”

Balachandran and colleagues discovered that when airway epithelial cells are infected with influenza virus, DAI senses viral RNA and becomes activated. DAI then communicates with the kinase RIPK3, which induces cell death driven by the effector proteins MLKL and FADD.

Mice lacking DAI were unable to control the spread of influenza virus and succumbed to lethal respiratory infection by the virus.

The discovery that influenza-infected cells altruistically self-destruct opens new doors for future research, with exciting therapeutic ramifications.

“Understanding the pathway is the first step to exploiting it,” Balachandran said.

This work was a collaboration between the Balachandran laboratory and laboratories at the University of Texas, St. Jude Children’s Hospital, and the Icahn School of Medicine at Mt. Sinai.

Fox Chase Cancer Center (Fox Chase), which includes the Institute for Cancer Research and the American Oncologic Hospital and is a part of Temple Health, is one of the leading comprehensive cancer centers in the United States. Founded in 1904 in Philadelphia as one of the nation’s first cancer hospitals, Fox Chase was also among the first institutions to be designated a National Cancer Institute Comprehensive Cancer Center in 1974. Fox Chase is also one of just 10 members of the Alliance of Dedicated Cancer Centers. Fox Chase researchers have won the highest awards in their fields, including two Nobel Prizes. Fox Chase physicians are also routinely recognized in national rankings, and the Center’s nursing program has received the Magnet recognition for excellence six consecutive times. Today, Fox Chase conducts a broad array of nationally competitive basic, translational, and clinical research, with special programs in cancer prevention, detection, survivorship, and community outreach. It is the policy of Fox Chase Cancer Center that there shall be no exclusion from, or participation in, and no one denied the benefits of, the delivery of quality medical care on the basis of race, ethnicity, religion, sexual orientation, gender, gender identity/expression, disability, age, ancestry, color, national origin, physical ability, level of education, or source of payment.

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