Women exposed to hepatitis C help Trinity researchers unlock secret to viral resistance

Scientists at Trinity College Dublin working with victims of a 40-year-old Irish health scandal believe they have found the potential secret to viral resistance.

The research team contacted over 100 women who were exposed to the hepatitis C virus after taking contaminated blood products in the late 1970s to investigate why some never showed symptoms.

They say their findings, which are based on a screen of the women’s immune systems, may explain why some people are able to resist viral infections and could help with the design of therapies to treat infected people.

Between 1977 and 1979, several thousand women were exposed to the hepatitis C virus through contaminated anti-D, a medication made using plasma from donated blood, provided by the State. Anti-D, which is given to Rhesus negative women who are pregnant with a Rhesus positive baby, prevents the development of antibodies that could be dangerous in subsequent pregnancies. However, some of the anti-D used during this period was contaminated with hepatitis C.

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From this outbreak, three groups of people were identifiable: those who were chronically infected; those who cleared the infection with an antibody response; and those who appeared protected against infection without making antibodies against hepatitis C.

“We hypothesised that women who seemed to resist HCV (hepatitis C virus) 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,” main author of the study Prof Cliona O’Farrelly, explained.

“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.”

Almost 40 women from the resistant group were recruited, alongside 90 women who were previously infected, according to the study, published in Cell Reports Medicine journal. In collaboration with the Institut Pasteur in Paris scientists invited almost 20 women in each group to donate a blood sample. This was stimulated with molecules that mimic viral infection and lead to activation of the innate immune system.

“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,” said Jamie Sugrue of Trinity’s school of biochemistry and immunology.

Normally, identifying resistant people is very difficult because they do not become sick after exposure to a virus. “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,” Sugrue explained.

The lab is now expanding its search for virus-resistant people by recruiting people who have been heavily exposed to Covid but never developed an infection.

An estimated 16,000 Irish women were exposed to potentially infectious batches of Anti-D. About 1,000 of them became infected with hepatitis C.