KU Researcher Finds Gene that Enhances Anti- Viral Immunity

Dr. Robin Orozco

LAWRENCE- Robin Orozco, an assistant professor of Molecular Biosciences at the University of Kansas, has unveiled new research that explores how a common mutation in the human population changes immune response during a virus infection. Dr. Orozco recently published these findings in PLoS Pathogens and provided foundational building blocks for researchers to better understand how this mutation is enhancing anti-viral immune function.

Orozco research focused on a mutation in a gene called PTPN22 which is present in about 5-15% of the North American population. Those with the mutated gene are at a higher risk for developing autoimmune diseases, particularly Type 1 Diabetes and Rheumatoid Arthritis.

Through the use of mouse models, Orozco was able to find that the mutated version of PTPN22 does enhance anti-viral immune cell function. This was observed in multiple immune cell types including the anti-viral CD4 T cells and dendritic cells.

The result of this research impacts multiple fields of science, as it “gives insight into how a common mutation in the human population, that is linked with disease, has a potentially beneficial impact during chronic virus infection. It shows that depending on the context, a mutation could be considered ‘good’ or ‘bad’.” Orozco said.

In particular, a commonality during chronic virus infection and cancer is T-Cell exhaustion. T-Cells – a type of white blood cell —become exhausted in response to chronic antigen stimulation, or when infection or cancer causes the body's immune system to stay active for a long time.

In the case of Dr. Orozco’s work, mouse models with the PTPN22 mutation have better T-Cell function.

Orozco said, “It is possible this is a new mechanism that prevents T-Cell exhaustion and could be used for therapeutic benefit.” Data from the report also shows that “the PTPN22 mutation is working in multi-cell way to enhance anti-viral immune cell function. Meaning, it isn’t just one cell type responsible. These factors add to the growing literature and foundational idea that anti-viral immunity is a complex, orchestrated, response, whose molecular details are still being teased out.”

In regard to the general public, Orozco’s work is foundational and gives the building blocks to better understand how this mutation is enhancing anti-viral immune function. A long-time goal of this research is to figure out how this mutation is enhancing anti-viral immune cell function and use that information to better design therapies for people who suffer from chronic virus infection.

Orozco began this work as a Post doctorate at Scripps Research in the lab of Dr. Linda Sherman, there Orozco was able to collaborate with multiple groups to accomplish her research and the creative freedom allowed to her over the course of per project was foundational to the creation of her own lab at KU. The research into the PTPN22 gene and its mutation was funded by NIH NIAID and by the University of Kansas. The majority of the research was completed at Scripps Research but was finalized in Orozco’s KU lab, where she was able to utilize the Flow Cytometry core.