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Protein with potential role in the fight against hepatitis C virus

An international team of researchers under Danish leadership is the first in the world to culture and purify an interferon (protein) called lambda 4 (IFNλ4) – a protein that behaves like Dr Jekyll and Mr Hyde. Paradoxically, it increases the risk of getting hepatitis C (HCV) and reduces the chances of being cured, but nevertheless has a potent effect against HCV in the laboratory. With these new results and further studies, the long-term hope is to stop the interferon’s negative effect and thereby achieve greater success in treating patients with hepatitis C.

2013.11.12 | Lisbeth Heilesen

An international team of researchers under Danish leadership is the first in the world to culture and purify an interferon that in due course could contribute to greater success in treating Hepatitis C. From left: Rune Hartmann, Ewa Terczynska-Dyla and Ole J. Hamming. (Photo: Lisbeth Heilesen)

The body produces the interferon IFN? during a viral infection. The family includes IFN?3 and, in some people, IFN?4. By studying how much intracellular and extracellular IFN?3 and IFN?4 exist, the Aarhus University research team discovered that the cells release much more IFN?3 than IFN?4. (Figure: Ole J. Hamming)

It has been known for a number of years that the ability of some people to spontaneously combat infection with hepatitis C (HCV) – and respond to treatment – is genetically determined. This ability is due to genetic differences in the part of the genome that contains lambda interferons (IFN?). Until now, however, nobody has known what these genetic differences mean.

A new interferon called IFN?4 was found in humans in early 2013. It turned out that the people who produce IFN?4 do not recover from HCV infection very well. What researchers did not know, however, was how this new interferon worked, and they were thereby unable to determine why it is harmful during HCV infection.

An international team led by researchers at Aarhus University therefore decided to find out how this interferon works. As the first in the world, they succeeded in culturing and purifying IFN?4, thereby gaining a unique opportunity to shed light on how this protein functions.

Their experiments showed that IFN?4 worked just as well as the other members of the IFN? family, and that they signalled the same way. However, there was a difference in the way IFN?4 was produced. While the other members of the IFN? family were released from the cells in large numbers, only a small amount of IFN?4 left the cells.

Even though the researchers thus came a long way in finding the answer to why people with IFN?4 do not recover well from HCV infection, their future experiments will now be targeted towards clarifying whether this difference in secretion can explain why they are poor at producing IFN?4 during HCV infection. By culturing and purifying IFN?4, however, the researchers have already made enormous progress.

Possible clinical application

Because IFN?4 is connected with a poor response to HCV, medicine aimed at IFN?4 is an obvious goal in the future. This could possibly stop the negative effect of IFN?4, enabling greater success in treating patients with HCV than the forms of treatment currently available.

The results have just been published in the international scientific journal The EMBO Journal.


Link to the article:

Interferon lambda 4 signals via the IFN? receptor to regulate antiviral activity against HCV and coronaviruses

Ole J Hamming1, Ewa Terczy?ska-Dyla1, Gabrielle Vieyres2, Ronald Dijkman3, Sanne E Jørgensen1, Hashaam Akhtar1, Piotr Siupka1, Thomas Pietschmann2, Volker Thiel3,4 and Rune Hartmann1

1Department of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark
2Institute of Experimental Virology,TWINCORE Centre for Experimental and Clinical Infection Research, Hannover, Germany
3Institute of Immunobiology, Cantonal Hospital, St Gallen, Switzerland
4Vetsuisse Faculty, University of Zurich, Zurich, Switzerland


Fact box

Interferons

Interferons (IFN) are small signal molecules that are produced during a viral infection. They signal the body’s cells that there is a virus, which makes the cells produce proteins that can prevent them from being infected.

Interferon can also be used in medical contexts to combat viral infections, including hepatitis C (HCV). Humans have a number of different genes for interferon. The IFN?4 gene was only recently discovered. It is of great interest because this gene negatively influences how well a person’s natural immune system combats infection with HCV, and also because the IFN?4 gene negatively affects treatment with interferon.


For more information, please contact

Postdoctoral Fellow Ole Jensen Hamming
Department of Molecular Biology and Genetics, Aarhus University, Denmark
ojh@mb.au.dk
, +45 2620 3159

or

Associate Professor Rune Hartmann
Department of Molecular Biology and Genetics, Aarhus University, Denmark
rh@mb.au.dk, +45 2899 2578

Public / media, Department of Molecular Biology and Genetics