Scientists uncover potential secret to viral resistance

Scientists have unearthed a secret that may explain why some people are able to resist viral infections, having screened the immune systems of women exposed to hepatitis C (HCV) through contaminated anti-D transfusions given over 40 years ago in Ireland.

The extraordinary work, just published in the journal Cell Reports Medicine, has wide-ranging implications from improving our fundamental understanding of viral resistance to the potential design of therapies to treat infected people.

Between 1977 and 1979 in Ireland, several thousand women were exposed to the hepatitis C virus through contaminated anti-D, which is a medication made using plasma from donated blood and given to Rhesus negative women who are pregnant with a Rhesus positive fetus. The medication prevents the development of antibodies that could be dangerous in subsequent pregnancies. Some of the anti-D used during the 1977–79 period was contaminated with hepatitis C.

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.

Scientists hypothesized 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 a first line of defense.

Then after a nationwide campaign over 100 women came forward to take part in the research work and scientists have gained some unique and important insights.The scientists ultimately recruited about 40 women from the resistant group, alongside 90 women who were previously infected.

They invited about 20 women in each group to donate a blood sample that they stimulated with molecules that mimic viral infection and lead to activation of the innate immune system.

By comparing the response of the resistant women to those who became infected, scientists 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 defense against viruses including hepatitis C and SARS-CoV-2, or COVID-19.

They inferred that the increased type I interferon production by the resistant donors, seen now almost 40 years after the original exposure to hepatitis C, is what protected them against infection.

The lab's efforts are now focused on leveraging these biological findings to unpick the genetics of viral resistance in the HCV donors. Their work on HCV resistance has already helped ignite international interest in resistance to other viral infections, including SARS-CoV-2, the virus that causes COVID-19.

The scientist group has expanded its search for virus-resistant individuals by joining in the COVID human genetic effort (www.COVIDhge.com) and by recruiting members of the public who have been heavily exposed to SARS-CoV-2 but never developed an infection (www.viralresistanceproject.com).

 Cliona O'Farrelly, Enhanced TLR3 responsiveness in hepatitis C virus resistant women from the Irish anti-D cohort, Cell Reports Medicine (2022). DOI: 10.1016/j.xcrm.2022.100804. www.cell.com/cell-reports-medi … 2666-3791(22)00363-9