The hepatitis B virus (HBV), which is up to 100 times more infectious than HIV, is primarily transmitted through blood or other bodily fluids. HBV infects liver cells and chronic infection can lead to serious health problems such as cirrhosis or liver cancer. According to the World Health organization, chronic hepatitis B affects nearly 240 million people worldwide, killing almost 800,000 people a year. Drugs are available to treat HBV, but they rarely cure the infection, and so the virus typically returns after the treatment ends. In a study published in Nature this week, an international team led by researchers from the Faculty of Medicine at the University of Geneva (UNIGE), Switzerland, discovered how our cells defend themselves against HBV infection, but also how the virus fights back. This work represents an important advance in our understanding of HBV and suggests new avenues for the development of innovative therapeutic agents.
A protective host protein destroyed by the virus X protein
Our cells produce a large number of defence proteins to protect us from viruses. These so-called «restriction factors» are a first line of defence against viral infections, and constitute an important component of the innate immune response. However, little is known about how our cells defend themselves against HBV, and which restriction factors (if any) are involved.
After infecting liver cells, the circular HBV genome travels to the cell nucleus, where it is remains, as a circle, independent from the cell chromosomes. But what happens next? This is what Professor Michel Strubin, a microbiologist at the Faculty of Medicine at UNIGE, in collaboration with the University of Lyon (France) and Gilead Sciences, Inc. (Foster City, California, USA), discovered. Their work revealed that a host protein complex (Smc5/6) recognizes the HBV genome and then acts as a restriction factor to prevent the production of new viruses.