Research has found that disruption of the actin cytoskeleton is key to stimulating the human immune response

Researchers from the Cleveland Clinic’s Florida Research and Innovation Center (FRIC) found that a disruption of the cellular structure, known as the actin cytoskeleton, is a “preparatory signal” for the body to respond to the virus. These results have been published in cell This week, the foundation is likely to be laid for the development of new antiviral vaccines and treatments.

Previously, viral genetic material such as RNA was considered the only requirement for certain sensor molecules living in cells to trigger an immune response – an “alarm system” for many types of cells. RNA also serves as the basis for vaccines by training a patient’s immune system to recognize the virus. This new study shows that the signaling process also requires disruption of the intracellular actin cytoskeleton, which occurs when the virus infects cells.

It’s a fundamental new way of looking at how the immune system is activated, and the implication is that this could lead to widespread antiviral therapies. Our data show that this process is common across different types of RNA viruses. “

Michaela Jack, Ph.D., Arthur and Marylin Levitt Chair and Scientific Director of FRIC

Cytoskeletons, made up of the actin protein, serve as structural support for cells but are also essential in processes such as the cell’s ability to grow, divide, and assimilate essential substances. Dr. Jack says the virus disturbs the cytoskeleton, but it can also happen to vaccine components and some treatments.

“Whether or not this process is sensed by our cellular immune surveillance system and can trigger an antiviral response,” says Dr. Jack. “Our work has shown that specific immune receptors sense virus-induced actin cytoskeleton rearrangements and then trigger the alarm.”

Although it has been around for decades, interest in using RNA as a basis for vaccines and treatments has grown exponentially during the COVID-19 pandemic. The research showed that the OS is similar across multiple viruses, including Zika and influenza or SARS-CoV-2, the virus that causes COVID-19.

Dr. Jack’s team, including lead author Dheeraj Acharya, PhD, a research associate at FRIC, has discovered that lipid components or virus-like molecules such as those used in vaccines or RNA-based therapies can cause the disruption of the cytoskeleton necessary for induction. immune response. These findings could help developers “tune” the immunostimulatory capabilities of treatments or vaccines.

Dr. Gack’s lab works within the Cleveland Clinic’s Global Multisite Center for Pathogen Research and Human Health, examining virus-host interactions at the molecular level, identifying host responses that could play a key role in developing new treatments and vaccines. The center is the cornerstone of the Cleveland District of Innovation.

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


Journal reference:

Acharya, Dr.; et al. (2022) Remodeling of the actin cytoskeleton leads to activation of RIG-I-like receptors. cell.