Properties of hepatitis B virus pre-S1 deletion mutants.
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| Abstract |
Deletion mutants of hepatitis B virus (HBV) pre-S proteins were detected in serum in 2 of 10 (20%) individuals with chronic hepatitis B infection following the initiation of interferon treatment. The size of these deletions was up to one-half of the entire pre-S1 region. In vivo, all HBV deletion mutants were found to coexist with a full-length "wild-type" viral genome. The functional properties of a HBV-deleted mutant were studied in detail and revealed a stop codon in the pre-S2 open reading frame in all 20 of the clones sequenced. Several of the deleted mutants produced low-level HBsAg in culture supernatants compared to wild-type virus due to a putative loss of transcription factor binding sites. Transfection experiments in human hepatoma cells (HuH-7) demonstrated that the polymerase gene function was not affected by the large pre-S1 deletions and mutant viral genomes were capable of replication. However, secretion of incapsidated mutant viral genomes was blocked in HuH-7 cells. Cotransfection studies with a plasmid expressing only the HBV pre-S1, pre-S2, and S proteins resulted in complete restoration of viral particle secretion. Our findings suggest that an in vivo trans-complementation phenomenon would have had to occur to permit secretion from the liver into serum of the nucleocapsids containing these deleted viral genomes.
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| Authors | M Melegari, S Bruno, J R Wands |
| Journal | Virology (Virology) Vol. 199 Issue 2 Pg. 292-300 (Mar 1994) ISSN: 0042-6822 [Print] United States |
| PMID | 8122362 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.) |
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