HBV z-bio 2021-02-15 303

　　Currently, about 260 million people (more than 3% of the global population) are chronically infected with hepatitis B virus (HBV); in the long run, this usually leads to complications such as liver cirrhosis and liver cancer, which cannot be cured by existing drugs. Scientists at the German Institute of Infection Research (DZIF) and Eppendorf University Hospital (UKE) have now studied a new combination therapy that has proven to be very effective in their infection model.

　　The new treatment method is based on shutting down the viral hepatitis B genome located in the nucleus of infected liver cells. After infecting liver cells, the viral genome is transformed into a closed circular DNA molecule in the nucleus. This DNA is a stable molecule called covalently closed circular DNA (cccDNA) and is used as a template for the production of new viruses. cccDNA represents the central repository of hepatitis B virus and allows it to persist in the liver. Virologist Dr. Maura Dandri and his research team at UKE tried to prevent HBV-cccDNA from producing other viruses in animal models.

　　The attack point of their therapy is the viral HBx protein, which prevents the host factor (SMC complex) from binding to it, thereby protecting the cccDNA in the nucleus from silence. On the one hand, the team used the antiviral cytokine IFN-α (which has been shown to reduce viral RNA) to treat animals, and on the other hand, they used RNA interference to inhibit the formation of HBx protein. In both cases, they are able to eliminate HBx production in most infected cells, thereby inactivating cccDNA through the reappearance of host restriction factors. In addition, they used this treatment in combination with bulevirtide to prevent HBV from entering the cells, thereby preventing re-infection. In this way, even after the treatment is over, the effect of cccDNA inactivation can be maintained.

　　Professor Dandri explained: “This combination therapy can achieve the continuous shutdown of cccDNA in infected cells.” Even though it was only tested in a mouse model, Professor Dandri believed the effect of this therapy: “The results show that through certain Combination therapy can shut down the HBV genome. These methods can now be used in clinical research to achieve the goal of curing chronic hepatitis B."