Posttranscriptional regulation of hepatitis B virus replication by the precore protein

Pier Paolo Scaglioni, Margherita Melegari, Jack R. Wands

Research output: Contribution to journalArticle

144 Citations (Scopus)

Abstract

Hepadnaviruses encode two core-related open reading frames. One directs the synthesis of the p21 core protein, which subsequently becomes a structural component of the viral nucleocapsid. The other produces a p25 precore protein that is targeted by a signal peptide to a cell secretory pathway where N-terminal processing will create a p22 species. This molecule will be further modified at the C-terminal region to generate p17, and the truncated protein is secreted from the cell as hepatitis Be antigen (HBeAg). The function of the precore gene in the biology of hepadnaviruses is unknown. We found that ablation of the precore gene resulted in the generation of a hepatitis B virus (HBV) species with a high-replication-level phenotype. More important, expression in trans of physiologic levels of p25 restored viral replication to wild-type levels. Moreover, transient or stable overexpression of the precore gene resulted in striking inhibition of HBV replication. The molecular species responsible for this viral inhibition effect was identified as the p22 nonsecreted HBeAg precursor protein. By sucrose gradient sedimentation analysis, we determined that expression of p22 leads to the formation of nucleocapsids similar to those made with wild-type p21 core protein. Immunoprecipitation experiments revealed that the p21 and p22 physically interact and form hybrid nucleocapsid structures devoid of pregenomic viral RNA. These experiments suggest that expression of the precore gene may be important in the regulation of HBV replication and describe a possible molecular mechanism(s) for this effect.

Original languageEnglish (US)
Pages (from-to)345-353
Number of pages9
JournalJournal of Virology
Volume71
Issue number1
StatePublished - 1997

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Hepatitis B virus
Virus Replication
virus replication
Nucleocapsid
Hepadnaviridae
nucleocapsid
Hepatitis B e Antigens
Proteins
proteins
Genes
Viral Structures
Protein Precursors
Secretory Pathway
Viral RNA
Protein Sorting Signals
Immunoprecipitation
gene overexpression
Open Reading Frames
Sucrose
signal peptide

ASJC Scopus subject areas

  • Immunology

Cite this

Scaglioni, P. P., Melegari, M., & Wands, J. R. (1997). Posttranscriptional regulation of hepatitis B virus replication by the precore protein. Journal of Virology, 71(1), 345-353.

Posttranscriptional regulation of hepatitis B virus replication by the precore protein. / Scaglioni, Pier Paolo; Melegari, Margherita; Wands, Jack R.

In: Journal of Virology, Vol. 71, No. 1, 1997, p. 345-353.

Research output: Contribution to journalArticle

Scaglioni, PP, Melegari, M & Wands, JR 1997, 'Posttranscriptional regulation of hepatitis B virus replication by the precore protein', Journal of Virology, vol. 71, no. 1, pp. 345-353.
Scaglioni, Pier Paolo ; Melegari, Margherita ; Wands, Jack R. / Posttranscriptional regulation of hepatitis B virus replication by the precore protein. In: Journal of Virology. 1997 ; Vol. 71, No. 1. pp. 345-353.
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