Fig. 2. Schematic representation of HBcrAg biogenesis²⁹.

Hepatitis B core antigen (HBcAg), translated from pre-genomic RNA (pgRNA), forms the icosahedral capsid inside complete and empty virions¹⁷⁹. The direct translation product from the precore mRNA is the precore precursor protein (p25), from which hepatitis B virus e antigen (HBeAg) and precore (PreC; also known as p22cr) are both derived. Removal of the N-terminal signal peptide of p25, by the signal peptidase during p25 translocation into the endoplasmic reticulum lumen, leads to the production of p22 (ref.¹⁸⁰), which is further processed at its C-terminal domain (CTD) before being secreted as the dimeric HBeAg (p17)^181,182. cccDNA, covalently closed circular DNA; HBc, hepatitis B c; HBcrAg, hepatitis B virus core-related antigen; NTD, N-terminal domain; ORF, open reading frame. Adapted with permission from ref.²⁹, American Society for Microbiology.