The small envelope protein is required for secretion of a naturally occurring hepatitis B virus mutant with pre-S1 deleted

Margherita Melegari, Pier Paolo Scaglioni, Jack R. Wands

Research output: Contribution to journalArticlepeer-review

65 Scopus citations


Naturally occurring deletions in the hepatitis B virus pre-S1 domain have been frequently found during persistent vital infection. In this study we have investigated the functional properties of a mutant viral genome that carries an in-frame deletion of 183 nucleotides in the pre-S1 region. This deletion removes the promoter of the small envelope gene. Transfection into human hepatocellular carcinoma cells of a replication-competent construct containing this deletion resulted in an increase of intermediate DNA replicative forms compared to those produced by wild-type hepatitis B virus. Northern hint analysis revealed that such cells lack the 2.1-kb transcripts encoding the small envelope protein and that hepatitis B surface antigen was absent as well. Furthermore, nucleocapsids containing the genome with pre-S1 deleted were not secreted, and the deleted large envelope protein was retained with the cytoplasm and exhibited a perinuclear pattern of distribution. However, coexpression with the small envelope protein was sufficient to restore virion secretion and to change the cellular distribution of the deleted large envelope protein. In addition, the creation of point mutations that prevent the synthesis of large or small envelope proteins also inhibited vital secretion and led to increased levels of hepatitis B virus intermediate replicative forms within the cell. These studies suggest that naturally occurring vital mutants with pre-S1 deletions involving the promoter region of the small envelope gene will generate a deleted large envelope protein that is retained in the endoplasmic reticulum, resulting in the accumulation of nucleocapsids containing vital DNA; transcomplementation with the wild-type small envelope protein will allow mutant virion secretion to occur.

Original languageEnglish (US)
Pages (from-to)5449-5454
Number of pages6
JournalJournal of virology
Issue number7
StatePublished - Jul 1997

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology


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