B 型肝炎ウイルスの持続感染を支えるウイルス因子 HBx 複合体の立体構造を解明～ウイルス遺伝子活性化の分子基盤を可視化～

HBx plays a pivotal role in HBV replication by enhancing cccDNA transcription. However, the HBx structure remains unsolved, representing a significant gap in knowledge. Here, we show the cryo-EM structure of HBx in complex with DDB1, which is a key complex for cccDNA transcription. In addition, HS-AFM revealed the dynamics of HBx in complex with DDB1. Our findings provide a comprehensive view of the structural, dynamic, and functional aspects of HBx and elucidate the key role of HBx in viral replication.

A cure for chronic hepatitis B requires eliminating or permanently silencing covalently closed circular DNA (cccDNA). A pivotal target of this approach is the hepatitis B virus (HBV) X protein (HBx), which is a key factor that promotes transcription from cccDNA. However, the HBx structure remains unsolved. Here, we present the cryoelectron microscopy structure of HBx in complex with DDB1, which is an essential complex for cccDNA transcription. In this structure, hydrophobic interactions within HBx were identified, and mutational analysis highlighted their importance in the HBV life cycle. Our biochemical analysis revealed that the HBx–DDB1 complex directly interacts simultaneously with NSE3, which is a component of the SMC5/6 complex, and Spindlin1. Additionally, HBx–DDB1 complex dynamics were explored via high-speed atomic force microscopy. These findings provide comprehensive insights into the structure and function of HBx in HBV replication.