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Proc Natl Acad Sci U S A. Nov 1988; 85(22): 8405–8409.
PMCID: PMC282466

A signal peptide encoded within the precore region of hepatitis B virus directs the secretion of a heterogeneous population of e antigens in Xenopus oocytes.


Using synthetic hepatitis B virus (HBV) mRNAs, we have shown that expression of HBV core-antigen gene sequences in Xenopus oocytes leads to the stable accumulation of 21-kDa cytoplasmic core protein (P21). In contrast, expression of precore plus core sequences leads mainly to the secretion of a heterogeneous population of proteins ranging in size from 15 to 22 kDa that collectively display viral e antigen (HBeAg) activity. We demonstrate that the precore region contains a cleavable 19 amino acid signal peptide that targets the precore proteins to the secretory pathway. The initial product of translocation (P22) is further processed during migration through the secretory pathway, apparently by a series of cleavage events at the arginine-rich carboxyl terminus, to yield multiple proteins of 15-18 kDa (P15-P18) that are secreted along with some P22. Our results indicate that serum HBeAg is generated by a signal peptide-mediated secretion event dependent on precore sequences.

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