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Florida Research and Innovation Center Team Discovers New Signal for Triggering Human Immune Response

Cytoskeleton disturbance is key in inducing immune response; multi-trigger immune system signaling holds implications for vaccines, therapeutics.


Researchers from Cleveland Clinic’s Florida Research and Innovation Center (FRIC) published findings in Cell this week which identified cytoskeleton disturbance as a “priming signal” for the body to respond to a virus.

RNA detection previously was considered the sole requirement for certain sensor molecules that live in cells to trigger an immune response – an “alarm system” for many types of cells. This study showed that the signaling process also requires perturbing the actin cytoskeleton, a protein network that supports cell structure.

Actin disturbance occurs when a virus infects host cells. “Whether this process is sensed by our cellular immune surveillance apparatus and can trigger an antiviral response has been unknown,” says Michaela Gack, PhD, the Arthur and Marylin Levitt Endowed Chair and Scientific Director of the FRIC. “Our work showed that specific immune receptors sense actin cytoskeleton rearrangements induced by viruses and then trigger alarm.”

The research, which comes during ongoing vaccine and therapeutics development for the COVID-19 pandemic, also holds implications for other viruses like Zika or the flu.

“It’s a fundamentally new way of considering how the immune system can be activated, and the implications are that this could lead to broad antiviral therapeutics,” Dr. Gack says. “Our data shows this process is common across different types of RNA viruses.”

Dr. Gack’s team, including lead author Dhiraj Acharya, PhD, research associate at FRIC, also discovered that lipid components – or virus-like particles such as those used in vaccines or RNA-based therapeutics – can cause the cytoskeletal disturbance necessary for prompting an immune response. These results could help developers “fine-tune” the immunostimulatory potencies of therapeutics or vaccines.

Dr. Gack’s lab, operating under Cleveland Clinic’s multi-site Global Center for Pathogen and Human Health Research, investigates virus-host interactions on a molecular level, identifying host responses that can play a key role in developing new treatments and vaccines.

The study was a collaboration with Konstantin Sparrer, PhD, Ulm University in Germany, and other collaborators from multiple institutions. Funding was provided by the U.S. National Institutes of Health, the Federal Ministry of Education and Research Germany, and the German Research Foundation.

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