New insights into viral resistance revealed

Scientists at Trinity College Dublin may have discovered why some people are able to resist viral infections. The team analyzed the immune systems of women exposed to hepatitis C (HCV) through contaminated anti-D transfusions administered over 40 years ago in Ireland. Their study has implications from improving our fundamental understanding of viral resistance to the potential development of new therapies for viral infections.

The findings, “Enhanced TLR3 Response in Hepatitis C Virus-Resistant Women from the Irish Anti-D Cohort,” are published in Cell Reports Medicine.

“Natural resistance to infection is an overlooked outcome after HCV exposure,” the scientists wrote. “Between 1977 and 1979, 1,200 Rhesus D-negative Irish women were exposed to HCV-contaminated anti-D immunoglobulin. Here, we investigate why some individuals appear to resist infection despite exposure (exposed seronegative [ESN]). We screen HCV resistant and susceptible donors for anti-HCV adaptive immune responses using ELISpots and VirScan to profile antibodies against all known human viruses.”

“We hypothesized that women who appeared to be 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,” explained Cliona O’Farrelly, PhD, professor of comparative immunology. . in the Trinity School of Biochemistry and Immunology, and lead author of the research paper.

“To test this, we needed to make contact with women exposed to the virus over 40 years ago and ask them to help us by allowing us to study their immune systems for scientific clues to explain their different responses.

“After a national campaign, more than 100 women came forward and we got some unique and important insights. The fact that so many women, many of whom have lived with medical complications for a long time, were willing to help is a testament to how much people want to get involved with science and help conduct research with the potential to generate genuine and positive impact. in society. We are deeply grateful to them.”

“By comparing the response of the resistant women with those who were infected, we found that the resistant donors had an enhanced type I interferon response after challenge. Type I interferons are a key family of antiviral immune mediators that play an important role in defense against viruses such as hepatitis C and SARS-CoV-2, or COVID-19,” said Jamie Sugrue, PhD candidate in the Faculty of Biochemistry and Immunology from Trinity. , and first author.

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

“These findings are important since resistance to infection is an overlooked outcome after a viral outbreak, mainly because it is very difficult to identify resistant people, since they do not get sick after viral exposure, not necessarily they would know they were exposed. This is 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 healthy population.”

Scientists are now focused on taking advantage of these to carefully analyze the genetics of viral resistance in HCV donors. His work on HCV resistance has generated international interest in resistance to other viral infections, including SARS-CoV-2.