Hepatitis B Virus (HBV) is a significant human pathogen that causes liver inflammation, cirrhosis, and hepatocellular carcinoma. One of the critical proteins encoded by HBV is the Hepatitis B Virus X protein (HBx), which plays a crucial role in the virus’s life cycle and its interaction with host cells .
HBx is a 154-amino acid protein that facilitates the efficient replication of HBV by stimulating HBV gene expression from the covalently closed circular DNA (cccDNA) template . The exact mechanisms by which HBx interacts with host proteins and facilitates HBV replication are still under investigation. However, it is known that HBx can interact with various host cellular factors to modulate viral and cellular gene expression .
HBx interacts with several host proteins, which can either promote or inhibit HBV replication. One such interaction is with the cellular protein CBFβ, which has been shown to inhibit HBV replication by blocking the formation of the HBx-CUL4-DDB1-SMC complex . This complex is essential for the degradation of the host restriction factor SMC5/6, which suppresses HBV transcription from the cccDNA template .
Another important interaction is with the novel X-associated cellular protein XAP2. XAP2 is a cytoplasmic protein that inhibits the transactivation function of HBx, thereby acting as a negative regulator of HBx . The interaction between HBx and XAP2 requires a small region on HBx containing amino acids 13–26 .
Recombinant HBx protein is produced using recombinant DNA technology, which involves inserting the HBx gene into an expression vector and introducing it into a host cell, such as Escherichia coli or yeast. The host cells then produce the HBx protein, which can be purified and used for various research purposes. Recombinant HBx protein is valuable for studying the interactions between HBx and host proteins, as well as for developing potential therapeutic interventions targeting HBx .
HBx is also implicated in the development of hepatocellular carcinoma (HCC). It acts as an indirect transcriptional transactivator, regulating the expression of many viral and cellular genes . HBx has been shown to promote cell proliferation and inhibit apoptosis, contributing to the development and progression of HCC . The exact mechanisms by which HBx contributes to HCC are still being elucidated, but it is clear that its interactions with host proteins play a significant role.