Hepatitis B Virus Vulnerability Uncovered: Potential for New Treatments

Researchers from The Rockefeller University, Memorial Sloan Kettering Cancer Center, and Weill Cornell Medicine have identified a key mechanism that allows the Hepatitis B virus (HBV) to infect liver cells. Published in *Cell*, the study reveals that HBV hijacks host chromatin structures to activate its genes. This discovery solves a long-standing mystery about HBV's biology and points to an anticancer drug candidate, CBL137, that may disrupt HBV's ability to establish long-lasting infection in liver cells. The research addresses the "chicken-and-egg" problem of HBV infection, where the viral protein HBx is needed for viral gene expression, but cannot be produced without it. The team found that the HBV X gene, which produces HBx, is sensitive to nucleosome formation, promoting its transcription. High-resolution nucleosome mapping confirmed that the HBV genome organizes similarly in infected liver cells. Testing five small molecules, the team found that CBL137 blocked HBx production at low doses, sparing human cells. This could potentially treat other chromatinized DNA viruses. Further animal model studies are planned to assess the drug's safety and efficacy, potentially marking a turning point in HBV treatment.