Experts uncover the secret of people’s viral resistance. Here’s why it matters

The study of the immune response to viral infections has been understood by screening the immune system of women who have been exposed to hepatitis C (HCV) by contaminated anti-D transfusions given over 40 years ago in Ireland.

The discovery may help to understand and advance the fundamental understanding of viral resistance to the potential development of treatments for the treatment of infected people.

Several thousand women in Ireland were infected with the hepatitis C virus between 1977 and 1979 as a result of contaminated anti-D, a drug given to rhesus negative pregnant women carrying rhesus positive fetuses made from plasma from blood donations. The drug stops the production of potentially harmful antibodies that could occur in subsequent pregnancies. Some of the anti-D used between 1977 and 1979 were contaminated with hepatitis C.

Three distinct populations emerged from this epidemic: people with chronic infection, those who were cured of infection by an antibody response, and those who appeared immune to infection but did not produce hepatitis C antibodies. .

Cliona O’Farrelly, professor of Comparative Immunology at Trinity School of Biochemistry and Immunology, is the senior author of the research paper. Cliona, who is based at the Trinity Biomedical Sciences Institute, said:

“We hypothesized that women who appeared resistant to HCV infection must have an enhanced innate immune response, which is the old part of the immune system that acts as the first line of defense.

“To test this, we needed to get in touch with women who were exposed to the virus more than forty years ago and ask them to help us by allowing us to study their immune systems to look for scientific clues that would explain their different responses.

“After a nationwide campaign, over 100 women came forward and we got unique and important insights. The fact that so many women – many of whom have been living with medical complications for a long time – have been willing to help shows how people want to engage in science and help pursue research that has the potential to have a real and positive impact on society, and we are deeply grateful to them.

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

Then, in partnership with the Pasteur Institute in Paris, they requested blood samples from nearly 20 women in each group, which they stimulated with molecules resembling a viral infection and causing the activation of the innate immune system.

Jamie Sugrue, a PhD candidate in Trinity’s School of Biochemistry and Immunology, is the first author of the research paper. He said:

“By comparing the response of resistant women to those who were infected, we found that resistant donors had an improved response to type I interferon after stimulation. Type I interferons are a key family of antiviral immune mediators that play an important role in defending against viruses, including hepatitis C and SARS-CoV-2 or COVID-19.

“We believe that the increased production of type I interferon by our resistant donors, observed now nearly 40 years after initial exposure to hepatitis C, is what protected them from infection.

“These results are important because resistance to infection is a much overlooked outcome after viral outbreak, mainly because it is very difficult to identify resistant individuals – since they do not get sick after viral exposure, they wouldn’t necessarily know they were exposed. That’s why cohorts like this, while tragic in nature, are so valuable – they provide a unique opportunity to study the response to viral infections in a population by elsewhere in good health.

The lab is currently focusing its efforts on using these biological findings 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 SARS-CoV-2 which causes COVID-19, globally.

(With ANI entries)