Expression mechanism of the hepatitis B virus (HBV) C gene and biosynthesis of HBe antigen

Jean-Jean, Olivier; Levrero, Massimo; Will, Hans; Perricaudet, Michel; Rossignol, Jean‐Michel

doi:10.1016/0042-6822(89)90356-5

Cited by 71 publications

(40 citation statements)

References 37 publications

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“…Proteolytic maturation is a necessary step for their activation or secretion to the extracellular medium. In the case of the HBe core protein of the hepatitis B virus, it involves cleavage of its 34 carboxy-terminal amino acids, in a region characterized by the presence of several groups of poly-arginine residues (20,22). As shown for other proteins (19), we hypothesized that the ubiquitously expressed furin, a TGN resident protease, or a related subtilisin family protease, was responsible for its primary processing, a conclusion further reinforced by the use of a furin inhibitor that blocked HBe maturation (21).…”

Section: Discussionmentioning

confidence: 99%

“…Furin-related serine proteases of the subtilisin family specific for polybasic residues are frequently responsible for this activity (18,19). The hepatitis B virus core protein HBe matures in the secretory pathway through a proteolytic process that liberates its carboxy-terminus and generates secretable forms (20). We have previously shown that when a class I epitope is inserted in this terminal region, antigen processing linked to the proteolytic maturation occurs in the secretory pathway, providing the antigenic peptide for class I loading and presentation (21).…”

Section: Received 10 April 2000 Revised and Accepted For Publicationmentioning

confidence: 99%

“…This proteolytic process generates a number of molecular forms detected intracellularly (mainly p25, p23, p22 and p17), the lightest of which are specifically secreted (20,22). In our previous report (21), we have shown how proteolytic maturation of a chimeric HBe protein harboring an antigenic epitope at its carboxy-terminus is able to yield peptides for MHC class I presentation in a TAP-independent manner.…”

Section: Furin Determines the Efficiency Of Proteolytic Maturationmentioning

confidence: 99%

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Generation of MHC Class I Peptide Antigens by Protein Processing in the Secretory Route by Furin

Gil‐Torregrosa

Castaño

López

et al. 2000

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Cytosolic degradation of endogenously synthesized proteins by the proteasome and translocation of processed peptides to the endoplasmic reticulum by the transporters associated with antigen presentation constitutes the classical route for antigen presentation by MHC class I proteins. We have previously defined an alternative pathway in the secretory route involving proteolytic maturation of precursor proproteins for chimeric hepatitis B virus secretory core protein HBe containing a class I epitope at its carboxy-terminus. We extend those results by demonstrating that intracellular delivery of the trans-Golgi network protease furin increases both proteolytic maturation and antigen presentation of the chimeric HBe proteins. An additional class I epitope from the HIV envelope gp160 protein was inserted into this COOH-terminal region of two different chimeric HBe proteins. This epitope was also presented to CTL in a transporter-independent manner involving furin, and protein maturation and antigen presentation were also enhanced by furin over-expression. Presentation of this second epitope was restricted by a different class I allele, thus suggesting that antigen presentation by this new pathway may apply to any antigenic epitope and class I molecule. These results define the furin proteolytic maturation pathway of HBe in the secretory route as a general antigen processing route for MHC class I presentation.

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Section: Discussionmentioning

confidence: 99%

Section: Received 10 April 2000 Revised and Accepted For Publicationmentioning

confidence: 99%

Section: Furin Determines the Efficiency Of Proteolytic Maturationmentioning

confidence: 99%

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Generation of MHC Class I Peptide Antigens by Protein Processing in the Secretory Route by Furin

Gil‐Torregrosa

Castaño

López

et al. 2000

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“…The precursor loses 19 amino-terminal aa and 36 (or 34 in several subtypes bearing a 6 bp shorter C gene) carboxyl-terminal aa for secretion from infected hepatocytes (Bruss & Gerlich, 1988 ;Jean-Jean et al, 1989). Although the biological function of HBeAg is still unclear, patients with the HBeAg marker generally have high levels of virus and higher rates of transmission than those who are anti-HBe-seropositive (Okada et al, 1976 ;Alter et al, 1976).…”

Section: Introductionmentioning

confidence: 99%

Reduced antigen production by hepatitis B virus harbouring nucleotide deletions in the overlapping X gene and precore-core promoter.

Moriyama

1997

Journal of General Virology

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“…Forty-eight h post-transfected cells were grown for 1 h in 10 ml of methionine-free cysteine-free Eagle's minimal essential medium (ICN), then for 3 h in 6 ml of methionine-free cysteine-free Eagle's minimal essential medium containing 500 Ci of Pro-Mix protein labeling mix (Amersham Pharmacia Biotech, specific activity Ͼ1,000 Ci/mmol). After labeling, media and cell extracts were prepared, and proteins were immunoprecipitated and analyzed as described previously (13,18).…”

Section: ϫ14mentioning

confidence: 99%

The C Terminus of the Hepatitis B Virus e Antigen Precursor Is Required for a Tunicamycin-sensitive Step That Promotes Efficient Secretion of the Antigen

Messageot¹,

Carlier²,

Rossignol

1998

Journal of Biological Chemistry

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The Hepatitis B virus encodes the secreted e antigen (HBe) whose function in the viral life cycle is unknown. HBe derives from a 25-kDa precursor that is directed to the secretory pathway. After cleavage of the signal sequence, the resulting 22-kDa protein (P22) is processed in a post-endoplasmic reticulum compartment to mature HBe by removal of the 34-amino acid C-terminal domain. The efficiency of HBe secretion is specifically decreased in cells grown in the presence of tunicamycin, an inhibitor of N-glycosylation. Inasmuch as HBe precursor is not N-glycosylated, our data suggest that a cellular tunicamycin-sensitive protein increases the intracellular transport through the HBe secretory pathway. The study of the secretion of HBe derived from C-terminal-truncated precursors demonstrates that the tunicamycin-sensitive secretion absolutely requires a part of the C-terminal region that is removed to form mature HBe, indicating that the cellular tunicamycinsensitive protein increases the efficiency of the intracellular transport of P22. We have also shown that the Escherichia coli ␤-galactosidase can be secreted when fused to the HBe precursor signal sequence and that the P22 C-terminal domain renders the secretion of this reporter protein also tunicamycin-sensitive.

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Expression mechanism of the hepatitis B virus (HBV) C gene and biosynthesis of HBe antigen

Cited by 71 publications

References 37 publications

Generation of MHC Class I Peptide Antigens by Protein Processing in the Secretory Route by Furin

Generation of MHC Class I Peptide Antigens by Protein Processing in the Secretory Route by Furin

Reduced antigen production by hepatitis B virus harbouring nucleotide deletions in the overlapping X gene and precore-core promoter.

The C Terminus of the Hepatitis B Virus e Antigen Precursor Is Required for a Tunicamycin-sensitive Step That Promotes Efficient Secretion of the Antigen

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