[Hepatitis B virus surface antigen: a multifaceted protein]

Despite the small size of its genome (3.2 kb) and having only four genes that are encoded within it, the hepatitis B virus (HBV) is one of the most successful viral pathogens in human history. It is estimated that there are about 350-400 million people worldwide who are chronically infected with HBV, and even with the extensive efforts that are being done with preventive vaccination, this malady still remains a clear and present danger to the public health. How is it possible that this small double-stranded DNA virus can escape and outfox the surveillance of the complex human immune system? One explanation is that HBV gene products play multiple roles in infections and throughout the viral life cycle so that the virus can effectively survive under various hostile circumstances. Indeed, the HBV DNA polymerase, for example, exerts several functions such as reverse transcription and RNA degradation, and the HBV X protein not only acts as a transcriptional activator, but it also interferes with the host cells' DNA repair mechanism as well as inducing apoptosis and controlling signal transduction. The HBV surface protein, which is encoded in the env gene, is another intriguing example of such multifunctionality. Thus, our present article overviews and summarizes the multifaceted role of this membrane protein as shown in 1) its role as a structural protein of the virus envelope; 2) its function as the viral ligand for interacting with the viral receptors on host cells; 3) its characteristics as an energy-independent transporter molecule that can mediate the nuclear accumulation of itself and other tagged molecules; 4) its role as a viral transactivator protein that can cause hepatocellular carcinoma; 5) its hypothetical function in viral apoptotic mimicry that results in host anti-inflammatory responses; and last 6) its immunostimulatory property by providing for strong and well-defined B- and T-cell epitopes. Understanding these various functions and the versatility of this single protein will help us decipher and understand the viral- and immuno-pathogenesis of HBV itself.