New research from the University of Kansas shows a “risk gene” linked to higher odds of developing autoimmune diseases, such as diabetes or lupus, may also provide a survival advantage fighting viral infections like coronavirus.
The research centers on a gene called PTPN22, which carries a mutation—1858C>T (R620W)—found in roughly one in 10 people in North America.
Previous research by the same team found that mice carrying the mutation are protected from chronic viral infection, as well as tumors.
“So, we were curious—if this mutation provides benefits in chronic conditions, what happens in an acute, potentially lethal infection?” said senior author Robin Orozco, assistant professor of molecular biosciences at KU, who oversaw the research.
To study this, Orozco and team used a mouse model of coronavirus infection that affects the liver and is lethal in about 50% of mice. According to the study results, published in PNAS, mice with the mutation were almost 100% protected from the lethal infection. The team found that the mutation enhances the function of natural killer cells in fighting coronavirus, a role that is not significant in mice without the mutation.
That finding led Orozco’s team to consider new therapeutic approaches.
“Instead of only focusing on cells that are already important, we might ask whether there are cells that appear unimportant but could become powerful if their function were enhanced,” she said. “In this case, boosting natural killer cell activity—specifically increasing interferon gamma, perforin and granzyme—made them effective against infection.”
Eeven when natural killer cells were removed from mutated mice, the animals still survived at high rates, despite higher viral loads. This suggests that other immune mechanisms contribute to survival.
The mutation’s effects may also have implications for autoimmunity, cancer and chronic infections, as well as emerging therapies that use natural killer cells.
“We’re now working to test whether the same mutation provides protection in lung infections, which are more relevant to respiratory viruses like SARS-CoV-2,” Orozco said. “Because immune responses differ by tissue, results in the liver may not directly translate to the lungs. Future work will examine how this mutation functions across different organs.”
Data from University of Kansas