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Scientists discover possible key to virus resistance

by Pragati Singh

Researchers from Trinity College Dublin unearthed a secret that may help to explain why some people are able to withstand viral infections after assessing the immune systems of women who were exposed to hepatitis C (HCV) through tainted anti-D infusions given more than 40 years ago in Ireland.
The new study, which was just published in the esteemed journal Cell Reports Medicine, has a wide range of implications, from improving our fundamental knowledge of viral resistance to the possible creation of therapeutics for infected patients. Between 1977 and 1979, thousands of women in Ireland were exposed to the hepatitis C virus by contaminated anti-D, a treatment given to Rhesus-negative mothers carrying Rhesus-positive foetuses. Anti-D is a therapy made from donated blood plasma.

The medication prevents the formation of potentially dangerous antibodies that might occur during subsequent pregnancies. Some anti-D used between 1977 and 1979 was contaminated with hepatitis C.

This outbreak produced three separate populations: those with a chronic infection, those cured of the sickness by an antibody response, and those who seemed immune to the disease but did not produce antibodies against hepatitis C.
The senior author of the study is Cliona O’Farrelly, Professor of Comparative Immunology at Trinity’s School of Biochemistry and Immunology.

“We hypothesised that women who seemed to resist HCV infection must have an elevated innate immune response, which is the oldest element of the immune system that works as the first line of defence,” Cliona, who is based at the Trinity Biomedical Sciences Institute, stated.
“To test this, we needed to contact ladies who had been exposed to the virus over forty years ago and ask them to aid us by enabling us to analyse their immune systems in search of scientific evidence that might explain their disparate reactions,” she continued.
Following a countrywide campaign, over 100 women came forward, providing us with some unique and essential insights.

The fact that so many women, many of whom have long lived with medical issues, were eager to assist demonstrates how much people want to connect with science and contribute to research that has the potential to have meaningful, good impacts on society. We owe them a great debt of gratitude.”
In the end, the researchers recruited 90 previously infected women and roughly 40 resistant individuals.
The researchers next obtained blood samples from roughly 20 women in each group, in collaboration with the Institut Pasteur in Paris. They are triggered by chemicals that mimic a viral infection and activate the innate immune system.

The study’s first author is Jamie Sugrue, a PhD candidate in Trinity’s School of Biochemistry and Immunology. “We discovered that resistant donors had an elevated type I interferon response following stimulation by comparing the reaction of the resistant women to those who were sick,” he added. Type I interferons are an essential family of antiviral immune mediators that aid in the defence against viruses such as hepatitis C and SARS-CoV-2, or COVID-19.”
“We believe that the enhanced type I interferon production by our resistant donors, visible today over 40 years after the original hepatitis C exposure, is what protected them from infection,” she added.

“These findings are significant because resistance to infection is a frequently neglected outcome following a viral epidemic, largely because identifying resistant individuals is difficult – because they do not feel ill after viral exposure, they may not be aware that they were infected. That is why, despite their devastating character, cohorts like this one are so valuable: they present a unique opportunity to study the response to viral infections in an otherwise healthy population.”

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