An estimated 71 million people worldwide are chronically infected with the hepatitis C virus. Chronic infection with the virus can lead to cirrhosis of the liver and ultimately to liver cancer.
The hepatitis C virus (HCV) was identified in 1988. It is transmitted almost exclusively via blood. Infection with HCV goes unnoticed in three-quarters of those affected and is a major cause of subsequent liver cancer.
Intense research is being carried out into HCV to understand the mechanisms of the virus-associated pathogenesis. Autophagy plays an important role in this: autophagy leads to a kind of recycling of the body’s cell components; whole cells or cell components are broken down and reused. It is also important for transport processes. Some viruses – including HCV – use autophagy to ensure they are released from the infected cells. The virus particles are released in the form of vesicles, resulting in a masking of the viruses.
It is known that HCV infection is associated with elevated levels of oxidative stress. HCV-induced oxidative stress plays an important role in the pathological processes associated with HCV infection, such as hepatic inflammation and liver cancer. The fact that oxidative stress triggers autophagy is physiologically significant, as oxidative stress describes a metabolic situation in which an excessively large amount of reactive oxygen compounds are formed, which may cause considerable damage, for example by damaging the DNA of the cells.
Prof. Eberhard Hildt, head of the Virology division, together with some of his colleagues, initially investigated why oxidative stress occurs in cells that contain HCV and what role oxidative stress plays in activating autophagy in HCV infections. They identified the transcription factor Nrf2 as a major player in this respect. Transcription factors are required for reading the genetic information. Nrf2 is an important regulator of the expression of cell-protecting genes and is one of the defence mechanisms of cells against oxidative stress. HCV inhibits Nrf2-mediated gene expression. The researchers discovered a previously unknown and complex mechanism by which HCV inhibits the Nrf2-dependent expression of cell-protecting genes, thus resulting in oxidative stress. They were able to shed light on the interaction between this unusual mechanism of inhibition of Nrf2, elevated oxidative stress, the triggering of autophagy, and its significance for the release of infectious viruses.
Updated: 07.08.2019
