Image: © Goffkein/Stock.adobe.com
By studying women who were exposed to hepatitis C many years ago, Trinity scientists were able to determine what causes viral resistance.
Scientists in Ireland have unearthed the potential secret as to why certain individuals are resistant to viral infections such as hepatitis or Covid-19.
A new study by researchers based in Trinity College Dublin (TCD) screened the immune systems of women who were exposed to the hepatitis C virus through contaminated transfusions more than 40 years ago.
In the late 1970s, several thousand women in Ireland were exposed to the virus through anti-D, a medication made using plasma from donated blood and given to Rhesus negative women who are pregnant with Rhesus positive foetuses. The medication prevents the development of antibodies that could be dangerous in subsequent pregnancies. However, some of the anti-D used in that period was contaminated with hepatitis C.
While some women were chronically affected by the disease, some others were able to overcome the infection with a natural antibody response. A third group of women appeared to have no symptoms of the disease and did not require antibodies to fight it.
“We hypothesised that women who seemed to resist [hepatitis C] infection must have an enhanced innate immune response, which is the ancient part of the immune system that acts as a first line of defence,” said Cliona O’Farrelly of Trinity’s School of Biochemistry and Immunology.
“To test this, we needed to make contact with women exposed to the virus over 40 years ago and ask them to help us by allowing us to study their immune systems to hunt for scientific clues that would explain their differing responses,” added O’Farrelly, who is the senior author of the study.
What caused the viral resistance?
After more than 100 women came forward for the study, the team ultimately recruited almost 40 women from the resistant group, alongside 90 women who were previously infected.
Blood samples of around 20 women in each group were then stimulated with molecules that mimic viral infection and lead to activation of the innate immune system. This was in collaboration with the Institut Pasteur in Paris.
By comparing the response of the resistant women to those who were infected, the scientists found that resistant donors had an “enhanced type I interferon” response after stimulation.
Jamie Sugrue, a PhD candidate in Trinity’s School of Biochemistry and Immunology and first author of the study, explained that type I interferons are a key family of antiviral immune mediators that play an important role in defending against viruses, including hepatitis C and Covid-19.
“We think that the increased type I interferon production by our resistant donors, seen now almost 40 years after the original exposure to hepatitis C, is what protected them against infection,” he said.
Published in the journal Cell Reports Medicine last week, the study has the potential to improve our fundamental understanding of viral resistance and help in the design of therapies to treat infected people.
“These findings are important as resistance to infection is very much an overlooked outcome following viral outbreak, primarily because identifying resistant individuals is very difficult. Since they do not become sick after viral exposure, they wouldn’t necessarily know that they were exposed,” said Sugrue.
“That’s why cohorts like this, though tragic in nature, are so valuable. They provide a unique opportunity to study the response to viral infections in an otherwise healthy population.”
10 things you need to know direct to your inbox every weekday. Sign up for the Daily Brief, Silicon Republic’s digest of essential sci-tech news.
