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The hepatitis B virus small envelope protein, commonly known as the small hepatitis B surface antigen (S-HBsAg), is the major envelope protein encoded by the S gene of hepatitis B virus (HBV)[5][2][3]. S-HBsAg is a polytopic membrane glycoprotein containing four transmembrane helices, an essential cytosolic loop with a zinc finger motif, and an extracellular N-terminus[4]. It is translated from the shortest of three transcripts of the S/preS gene region and forms the backbone of the viral envelope as well as the abundant non-infectious subviral particles secreted during infection[2][6]. S-HBsAg plays critical roles in viral particle assembly, virus entry into hepatocytes, and modulation of the host immune response[3][2]. High levels of HBsAg in patient serum are a hallmark diagnostic marker for acute and chronic HBV infection, and its clearance is considered an indicator of functional cure[6]. S-HBsAg also serves as the main immunogen in licensed HBV vaccines[3]. Dysregulation of its expression and chronic persistence are associated with liver inflammation, immune dysfunction, and a risk of hepatocellular carcinoma[2].
Immune neutralization (antibody binding to HBsAg in vaccination or therapy), RNA degradation (antisense mechanisms targeting HBsAg mRNA)
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