A groundbreaking collaboration between The Rockefeller University, Memorial Sloan Kettering Cancer Center (MSK), and Weill Cornell Medicine has unraveled the molecular mechanisms behind hepatitis B virus (HBV) infection. Researchers have discovered that HBV hijacks host chromatin structures to activate its own genes, providing a potential solution to the long-standing chicken-and-egg problem of viral gene expression.
The study, published in Cell, reveals that the virus’s X gene is particularly sensitive to nucleosome formation, allowing it to express its genes despite host cell defenses. This mechanism enables HBV to establish persistent infection in liver cells.
Researchers used high-resolution nucleosome mapping to analyze how HBV’s DNA interacts with host histones to form chromatin structures. Their findings confirm that the presence of nucleosomes on the viral genome is necessary for transcription of the X protein.
The discovery sheds new light on the basic biology of a virus affecting 300 million people worldwide and may lead to sorely needed therapies. A small molecule compound, which also acts as an anticancer drug candidate, was found to block HBx protein production in liver cells at relatively low doses.
This breakthrough highlights the potential for “basic science” research to drive medical advances. The collaboration between institutions brought together necessary expertise and technological resources, demonstrating the power of interdisciplinary research in solving complex biological puzzles.
The study’s authors emphasize that their findings could have significant implications for HBV treatment, potentially offering a new approach to targeting the virus at its root rather than just suppressing its replication. Future studies will focus on testing this compound candidate in animal models to determine its safety and efficacy.
Source: https://www.rockefeller.edu/news/37396-how-solving-a-hepatitis-b-paradox-opened-the-door-to-new-therapies