IMMUNOLOGY

Researching the genetic basis for resistance to HCV infection

TCD scientists are researching the genetic basis for reported resistance in some women to HCV infection following anti-D contamination, and are seeking volunteers

Dr Cliona O'Farrelly, Professor of Comparative Immunology, Trinity College, Dublin

November 3, 2016

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  • two hepatitis C virus (HCV) outbreaks have occurred in women in Ireland as a result of HCV-contaminated anti-D immunoglobulin; the first outbreak occurred between 1977 and 1979, and the second between 1991 and 1994.

    Researchers at TCD are now seeking volunteers who were exposed to anti-D contaminated with the hepatitis C virus (HCV) between 1977 and 1979 in an attempt to discover why some people are naturally protected from HCV infection, while others are not. 

    The research, it is hoped, may aid the development of new antiviral therapies and vaccines. There is currently no vaccine for hepatitis C and although new antiviral medicines available in recent years can cure up to 90% of patients with hepatitis C infection, these therapies are expensive.

    Hepatitis C was not identified until 1989. Prior to this, it was known as non-A, non-B viral hepatitis. The virus targets, invades and gradually damages the liver causing liver cirrhosis. Up to 20% of those chronically infected will develop cirrhosis of the liver over a 20 to 25-year period. Approximately 3-4% of patients with cirrhosis will develop hepatocellular carcinoma (HCC) per year.

    The study

    Over 1,000 women were infected with HCV in Ireland due to HCV-contaminated anti-D immunoglobulin. The TCD researchers have pointed out that of these women, approximately half had evidence of past infection (antibodies) but no circulating virus, while the other half developed chronic infection.

    During the 1977-1979 outbreak, 50% of women who received high-risk HCV-contaminated anti-D batches were infected, but the rest of the women who received these high-risk batches were resistant to this infection.

    According to professor of comparative immunology at TCD, Cliona O’Farrelly, this means these women must have been naturally protected from the virus. “We believe these women may have a ‘super’ immune system that is able to fight viral invaders. We now want to find out why – and how – this system does such a good job.”

    To do this, Prof O’Farrelly and her team will look at the information stored within the genes of naturally HCV resistant people. The team will then compare it to the information from the genes of people who are unable to resist infection. The researchers say by understanding how Irish women were able to resist hepatitis C virus, it is hoped to uncover the mechanism that provides protection against viral infections. “If we unravel the mysteries of this mechanism, we can try to harness it to create successful vaccines, not only against HCV but perhaps against other recalcitrant viruses. We may also be able to create new antiviral therapies against not just one, but many different viruses,” Prof O’Farrelly says.

    “We aim to study women who received contaminated anti-D but who weren’t infected (ie. who tested negative for antibodies against hepatitis C virus and negative for HCV nucleic acid). In this study we will be trying to identify specific genetic markers, which are present in resistant women’s DNA, that indicate resistance to hepatitis C virus infection. We will then study the function of those genes. To do this we also need to study women who were infected by contaminated anti-D.”

    Women who became infected with HCV as well as those who still show no signs of infection despite exposure are invited to participate. The researchers have pointed out that participation in the study is easy, and non-invasive, and the research could have a major impact on fighting viruses. 

    All that is needed is a saliva sample, which can be easily collected at home and mailed to the research team at TCD.

    At this stage the study will be focusing on women who received contaminated anti-D batches between the years of 1977-1979. This is because the two outbreaks (in 1977-1979 and 1991-1994) involved different types of hepatitis C virus – a genotype 1 virus in 1977-1979 and a genotype 3 virus in 1991-1994. This difference may affect the results of the study. The TCD researchers say they may well include women exposed between 1991-1994 in future studies. 

    Women who may be interested in participating or would like to receive further information, are asked to contact the researchers by Tel: 087 7913600 or email: TCDStudy2016@tcd.ie. They can also visit the TCD website for more information:
    www.tcd.ie/Biochemistry/research/cig_hepatitisc.php 

    The project is funded by Science Foundation Ireland and is led by Cliona O’Farrelly, professor of comparative immunology at Trinity College Dublin. Team members working on this project include Dr Mark Robinson, postdoctoral research fellow, Dr Lena Fischer, postdoctoral research fellow, and Margaret Needham, research associate

    © Medmedia Publications/Hospital Doctor of Ireland 2016