The secret of viral drug resistance hidden behind medical malpractice 40 years ago

These findings have significant implications, including the potential
to improve our understanding of viral drug resistance and to design therapies to treat infected people.

Researchers at Trinity College Dublin have a finding that could explain why some people are able to fight off viral infections
.
They did this
by screening the immune systems of women exposed to hepatitis C (HCV) who had been injected contaminated anti-D antibodies in Ireland more than 40 years ago.
The findings, recently published in the journal Cell Reports Medicine, have important implications
for our understanding of viral resistance and the development of therapies to treat infected people.

Between 1977 and 1979, thousands of women in Ireland were exposed to the hepatitis C virus
through contaminated anti-D antibodies.
Anti-D antibodies, a drug made from plasma from donated blood, are injected into Ganga-negative women with Ganges virus-positive fetuses
.
This medicine prevents the production of antibodies because antibodies can be dangerous
to the fetus.
However, some anti-D drugs used in 1977-79 were contaminated
with hepatitis C.

The outbreak identified three groups of people: chronically infected; Those who clear the infection through an antibody response; and those who
did not develop antibodies to hepatitis C.

Cliona O'Farrelly, professor of comparative immunology in Trinity College's School of Biochemistry and Immunology, is the senior author
of the research paper.

Cliona, from Trinity College's Institute of Biomedical Sciences, said: "We hypothesized that women who appeared to be able to fight HCV infection must have a stronger innate immune response, an ancient part of the immune system, as the first line
of defence.
To test this, we need to reach out to women who were exposed to the virus more than 40 years ago and ask them to help us study their immune systems for scientific clues to explain their different responses
.
”

She continued: "After a nationwide campaign with more than 100 women coming forward, we gained some unique and important insights
.
The willingness of so many women – many of whom have long suffered from medical complications – to help is a testament to how much people want to get involved in science and help conduct research
that has the potential to have a real positive impact on society.
We are deeply grateful
to them.
”

The scientists eventually recruited nearly 40 women from the resistance group, as well as 90 women who had been previously infected
.

In collaboration with the Institute t Pasteur in Paris, they invited nearly 20 women in each group to donate a blood sample, which they stimulated with molecules that mimicked viral infections to activate the innate immune system
.

Jamie A.
Sugrue, a doctoral candidate in Trinity College's School of Biochemistry and Immunology, is the first author of
the research paper.
"By comparing responses in resistant and infected women, we found that resistant donors had an enhanced type I interferon response
after stimulation," he said.
Type I interferons are a key class of antiviral immune mediators that play an important role
in defending against viruses such as hepatitis C and SARS-CoV-2 or COVID-19.
We believe that nearly 40 years after initial exposure to hepatitis C, our resistant donors have increased the secretion of interferon type I, which is what
protects them from infection.
These findings are important because resistance to infection is largely an overlooked outcome after a virus outbreak, largely because identifying resistant individuals is very difficult — because they don't get sick after being exposed to the virus, and they don't necessarily know they're infected
.
That's why such cohorts, while tragic in nature, are so valuable – they provide a unique opportunity to study how healthy people respond to
viral infections.
”

The lab's current work is focused on using these biological findings to decipher viral resistance genes
in HCV donors.
Their work on HCV resistance has helped spark international interest in resistance to other viral infections, including the SARS-CoV-2 virus
that causes COVID-19.

References:

Enhanced TLR3 responsiveness in hepatitis C virus resistant women from the Irish anti-D cohort” by Jamie A.
Sugrue, Céline Posseme, Ziyang Tan, Christian Pou, Bruno Charbit, Vincent Bondet, Nollaig M.
Bourke, Petter Brodin, Darragh Duffy and Cliona O’Farrelly, 4 November 2022, Cell Reports Medicine.