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Freiburg scientists in collaboration with Berlin researchers detect molecular scars in immune cells after successfully treated hepatitis C infection / Publication in Nature Immunology

The World Health Organization (WHO) estimates that around 70 million people worldwide are affected by chronic hepatitis C infection. Thanks to highly effective, directly antiviral substances, the disease is now curable. However, it was previously unclear whether the body's own immune response would also recover after successful treatment. Researchers at the Medical Center - University of Freiburg in collaboration with the Charité in Berlin have now been able to show that scars remain in killer T cells. This allows conclusions to be drawn about the mode of action of killer T cells in re-infections with hepatitis C and other chronic diseases. The research results were published on Monday, January 4, 2021 in the online edition of the renowned journal Nature Immunology.

Nobel Prize-winning therapeutic approach shows effect

In around 70 percent of all infected people, the virus-specific immune response against hepatitis C viruses (HCV) fails. This results in chronic infections that lead to inflammation of the liver, severe secondary diseases and significantly increased mortality. "An important step towards solving this global health problem was the introduction of highly effective, directly antiviral substances that have made it possible to cure chronic HCV infections for the first time," explains Prof. Dr. Robert Thimme, Medical Director of the Department of Medicine II at the Medical Center - University of Freiburg. "The significance of this medical success story is underlined by the award of this year's Nobel Prize for Medicine to Harvey J. Alter, Michael Houghton and Charles M. Rice, whose work was instrumental in the development of the therapy."

Permanent damage despite successful therapy

The question of how such therapy with direct acting antivirals (DAA) affects the immune system remains unanswered. Does the virus-specific immune response also recover after years of chronic HCV infection? Scientists at the Medical Center - University of Freiburg led by Thimme and Dr. Maike Hofmann, in collaboration with Dr. Naveed Ishaque from the Charité in Berlin, have now been able to show that traces remain in the immune system even after successful therapy. "We were able to detect scars in the so-called killer T cells, which are responsible for the direct defense against virus-infected cells. These scars were characterized by a molecular pattern that was already evident during chronic hepatitis C infection and is associated with a lower effectiveness of killer T cells in defending against the virus," reports Hofmann. She is a research group leader at the Department of Medicine II and is supported by the Margarete von Wrangell Habilitation Program for Women of the State of Baden-Württemberg, among others.

Effect of scars on recurrent infections

"Our findings are particularly important for the treatment of recurrent infections with hepatitis C viruses, which are unfortunately not uncommon in high-risk groups. Our next step will therefore be to take a closer look at the effect of molecular scars during re-infections with HCV," Thimme announces. The findings are also relevant for understanding other diseases: "The insights we have gained allow us to draw conclusions about the mode of action of killer T cells in other chronic viral infections such as HIV or hepatitis B, but also in tumor diseases," says Hofmann. The German Research Foundation is funding translational research into HCV infection as part of the Transregio 179 Collaborative Research Center at the Universities of Freiburg, Heidelberg and Munich.

Original title of the study: Memory-like HCV-specific CD8+ T cells retain a molecular scar after cure of chronic HCV infection

DOI: 10.1038/s41590-020-00817-w

Link to the study:www.nature.com/articles/s41590-020-00817-w

Contact:
Dr. Maike Hofmann
Research group leader
Department of Medicine II
Uniklinik Freiburg
maike.hofmann@uniklinik-freiburg.de