After screening the immune systems of women who were exposed to hepatitis C (HCV) through contaminated anti-D transfusions given more than 40 years ago in Ireland, researchers from Trinity College Dublin have discovered a secret that may help to explain why some people are able to resist viral infections.

The groundbreaking research, which was just published in the prestigious journal Cell Reports Medicine, has numerous ramifications, ranging from advancing our fundamental understanding of viral resistance to the potential development of treatments for the treatment of infected individuals.

Several thousand women in Ireland were infected with the hepatitis C virus between 1977 and 1979 as a result of tainted anti-D, a drug administered to Rhesus-negative pregnant women carrying Rhesus-positive foetuses that are manufactured from plasma from donated blood.

The drug stops the production of potentially harmful antibodies that could arise during later pregnancies. Some of the anti-D used between 1977 and 1979 had hepatitis C contamination.

Three distinct populations emerged from this outbreak: those with a chronic infection, those who were cured of the infection by an antibody response, and those who appeared immune to infection without producing antibodies against hepatitis C.

Cliona O'Farrelly, professor of Comparative Immunology at Trinity's School of Biochemistry and Immunology, is the senior author of the research article.

Cliona, who is based at the Trinity Biomedical Sciences Institute, said: "We hypothesised that women who seemed to resist HCV infection must have an enhanced innate immune response, which is the ancient part of the immune system that acts as the first line of defence."

"To test this we needed to make contact with women exposed to the virus over forty 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."

"After a nationwide campaign over 100 women came forward and we have gained some unique and important insights. That so many women -- many of whom have lived with medical complications for a long time -- were willing to help is a testament to how much people want to engage with science and help pursue research with the potential to make genuine, positive impacts on society. We are deeply grateful to them."

In the end, the researchers picked up 90 previously infected women and nearly 40 members of the resistant group.

Then, in partnership with the Institut Pasteur in Paris, they requested blood samples from nearly 20 women in each group, which they stimulated with molecules that resemble a viral infection and cause the innate immune system to become active.

Jamie Sugrue, a PhD candidate in Trinity's School of Biochemistry and Immunology, is the first author of the research article. He said: "By comparing the response of the resistant women to those who became infected, we found that resistant donors had an enhanced type I interferon response after stimulation. Type I interferons are a key family of antiviral immune mediators that play an important role in defence against viruses including hepatitis C and SARS-CoV-2, or 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."

"These findings are important as resistance to infection is very much an overlooked outcome following the 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. 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."

The lab is currently concentrating its efforts on using these biological discoveries to dissect the genetics of viral resistance in HCV donors. Their research on HCV resistance has already sparked interest in other viral diseases, such as COVID-19-causing SARS-CoV-2, on a global scale.