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Chronic hepatitis B virus (HBV) infection afflicts millions worldwide with cirrhosis and liver cancer. HBV e-antigen (HBeAg), a clinical marker for disease severity, is a nonparticulate variant of the protein (core antigen, HBcAg) that forms the building-blocks of capsids. HBeAg is not required for virion production, but is implicated in establishing immune tolerance and chronic infection. Here, we report the crystal structure of HBeAg, which clarifies how the short N-terminal propeptide of HBeAg induces a radically altered mode of dimerization relative to HBcAg (∼140° rotation), locked into place through formation of intramolecular disulfide bridges. This structural switch precludes capsid assembly and engenders a distinct antigenic repertoire, explaining why the two antigens are cross-reactive at the T cell level (through sequence identity) but not at the B cell level (through conformation). The structure offers insight into how HBeAg may establish immune tolerance for HBcAg while evading its robust immunogenicity.

Original publication

DOI

10.1016/j.str.2012.10.017

Type

Journal article

Journal

Structure

Publication Date

08/01/2013

Volume

21

Pages

133 - 142

Keywords

Capsid, Capsid Proteins, Crystallography, X-Ray, Hepatitis B Core Antigens, Hepatitis B e Antigens, Hepatitis B virus, Immune Evasion, Molecular Mimicry, Protein Multimerization, Protein Precursors, Protein Structure, Quaternary, Protein Structure, Secondary