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Hepatitis B virus e antigen (HBeAg) is a secreted, non-particulate protein encoded by the HBV precore/core gene, distinct from the intracellular core antigen (HBcAg) despite sharing most of their sequence. It arises from translation of a longer precore mRNA, with the N-terminal precore extension acting as a signal peptide that directs the protein through the secretory pathway, where it undergoes cleavage to form mature dimers stabilized by intramolecular disulfide bonds.[1][2][5] This results in a unique conformation that precludes capsid assembly and creates distinct B-cell epitopes, while retaining T-cell cross-reactivity with HBcAg.[2][5] Biologically, HBeAg plays a key role in immune modulation, promoting tolerance to HBV antigens and enabling persistent infection during the high-viremia, immune-tolerant phase.[1][4][5] In disease, HBeAg positivity marks highly infectious chronic HBV carriers, with seroconversion to anti-HBe signaling reduced replication, though often accompanied by precore/core promoter mutants that evade immunity.[1][4] No direct small-molecule drugs target HBeAg, but it serves as a critical biomarker for disease phase, prognosis, and treatment decisions in HBV management.[1][3]
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