The interferon-stimulated gene C19orf66 plays an important role in the defence against hepatitis C viruses. A research team at Ruhr-Universität Bochum (RUB) headed by Professor Eike Steinmann from the Department for Molecular and Medical Virology has now studied how C19orf66 works. The results show that C19orf66 disrupts the formation of the viral replication machinery.

The researchers published their study on 12 April 2020 in the Journal of Hepatology.

Hepatitis C patients produce more of the gene than healthy individuals

"In order to find out whether the C19orf66 gene is increasingly activated in samples from hepatitis C patients, we first examined liver tissue samples from infected and healthy people," explains PhD student Volker Kinast. The analysis showed that the production of C19orf66 is increased in hepatitis C patients.

"In the next step, we checked whether C19orf66 has an antiviral effect against hepatitis C viruses. We conducted experiments using cells that contained a lot of C19orf66 and cells that contained only a little of it. We then observed that the hepatitis C virus replicates much more slowly in cells that contain a lot of C19orf66 than in control cells," says Kinast.

Virological and molecular biological analyses

Additional experiments with cells in which the gene C19orf66 was completely switched off confirmed: C19orf66 inhibits the replication of the hepatitis C virus. In order to understand how C19orf66 does this, the researchers conducted numerous virological and molecular biological analyses.

The results show that C19orf66 disrupts the formation of the viral replication machinery. The hepatitis C virus has the ability to manipulate liver cells in such a way that an accumulation of membrane vesicles occurs within the cell. The virus uses these membrane vesicles as a scaffold to replicate effectively. C19orf66 disrupts and alters the structure of the scaffold and thus inhibits the replication of the virus.

Many people don't know that they are infected

An estimated 71 million people have a chronical hepatitis C infection, and a large percentage of them are not aware of this fact. Over the years, the virus damages the liver, resulting in severe liver disease that often requires liver transplantation.

Funding

The study was founded by the Helmholtz-Alberta-Initiative -- Infectious Disease Research (HAI-IDR), the Swiss National Science Foundation (310030B_147089) and the German Research Foundation (TRR179, TP9).

Story Source:

Materials provided by Ruhr-University Bochum. Original written by Raffaela Römer; translated by Donata Zuber. Note: Content may be edited for style and length.

Journal Reference:

1. Volker Kinast, Agnieszka Plociennikowska, Anggakusuma, Thilo Bracht, Daniel Todt, Richard JP. Brown, Tujana Boldanova, Yudi Zhang, Yannick Brueggemann, Martina Friesland, Michael Engelmann, Gabrielle Vieyres, Ruth Broering, Florian W.R. Vondran, Markus H. Heim, Barbara Sitek, Ralf Bartenschlager, Thomas Pietschmann, Eike Steinmann. C19orf66 is an interferon-induced inhibitor of HCV replication that restricts formation of the viral replication organelle. Journal of Hepatology, 2020; DOI: 10.1016/j.jhep.2020.03.047