Biochemical and Biophysical Properties of Hepatitis B Core Particles Derived from Dane Particles and Infected Hepatocytes

Ha, Fields; Fb, Hollinger; Desmyter, Jan; Jl, Melnick; Gr, Dreesman

doi:10.1159/000148909

Cited by 20 publications

(10 citation statements)

References 13 publications

(22 reference statements)

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“…The approximate sedimentation coefficient was calculated using the tables previously described by C. R. McEwen (35), where an average density in sucrose of 1.1 g/ml was used for the supernatant HCV particles and the described density of 1.2 g/ml (27) was used for HBV core particles. The approximate sedimentation coefficient of HBV core particles was ϳ100S, in good agreement with the expected coefficient (16). The Stokes radius calculated for HBV core particle is ϳ36 nm, as observed previously (13).…”

supporting

confidence: 88%

Differential Biophysical Properties of Infectious Intracellular and Secreted Hepatitis C Virus Particles

Gastaminza

Kapadia

Chisari

2006

J Virol

215

232

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The recent development of a cell culture infection model for hepatitis C virus (HCV) permits the production of infectious particles in vitro. In this report, we demonstrate that infectious particles are present both within the infected cells and in the supernatant. Kinetic analysis indicates that intracellular particles constitute precursors of the secreted infectious virus. Ultracentrifugation analyses indicate that intracellular infectious viral particles are similar in size (ϳ65 to 70 nm) but different in buoyant density (ϳ1.15 to 1.20 g/ml) from extracellular particles (ϳ1.03 to 1.16 g/ml). These results indicate that infectious HCV particles are assembled intracellularly and that their biochemical composition is altered during viral egress.Hepatitis C virus (HCV) is a major cause of chronic hepatitis worldwide. Approximately 3% of the human population is infected, and more than 80% of all HCV infections progress to chronicity, ultimately leading to fibrosis, cirrhosis, and hepatocellular carcinoma (24). There is no vaccine against HCV, and the most widely used therapy involves the administration of type I interferon (␣2A) combined with ribavirin. However, this treatment strategy is toxic and has been shown to be ineffective in a significant proportion of the cases (41).HCV is a member of the Flaviviridae family and the sole member of the genus Hepacivirus (34). HCV is an enveloped virus with a single-strand positive RNA genome that codes for a unique polyprotein of approximatively 3,000 amino acids (11,12). A single open reading frame is flanked by 5Ј and 3Ј untranslated regions that contain RNA sequences essential for RNA translation and replication, respectively (17,18,23). The translation of the single open reading frame is driven by an internal ribosomal entry site sequence present within the 5Ј untranslated region (23), and the resulting polyprotein is processed by cellular and viral proteases into its individual components (reviewed in reference 42). The E1, E2, and core structural proteins are assembled into particles (3, 4), but are not essential for viral RNA replication or translation. The NS2, NS3, NS4A, NS4B, NS5A, and NS5B nonstructural proteins constitute the viral components necessary for efficient viral RNA replication, although NS2 is dispensable for this function (5, 33). In the linear sequence of the polyprotein, the structural proteins are separated from the nonstructural proteins by a small hydrophobic protein, p7 (29), whose function remains unknown but that has the potential to form ion channels (19). Viral proteins are localized in the cytoplasm, and it is assumed, by analogy with other members of the Flaviviridae family, that the entire life cycle of the virus is exclusively cytoplasmic (32).

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supporting

confidence: 88%

Differential Biophysical Properties of Infectious Intracellular and Secreted Hepatitis C Virus Particles

Gastaminza

Kapadia

Chisari

2006

J Virol

215

232

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“…These preliminary observations and the physical instability of core particles, referred to by Budkowska [12], prompted us to pursue the details of the degra dation process of the core particles by physical rather than chemical means to see whether the loss of HBc antigenicity is followed by a loss of polypeptide composition. Many reports have been presented con cerning the proteins of either Dane particlederived core particles [1,11,13] or those ob tained from HBV-infected human liver [14,15] and chimpanzee liver [13], Considerable vari ations in the kinds and molecular sizes of the core particles have been demonstrated in these reports. In our study both the core particle starting suspension and the column-purified core suspension revealed a homogenous dis tribution of dense core particles, as was sup ported by a density of 1.358 g/ml, and both materials had an electrophoretically simple protein composition, consisting of a predomi nant protein with a molecular weight of 20,000 and a minor protein of molecular weight 43,000.…”

Section: Discussionmentioning

confidence: 99%

Antigenic Conversion from HBeAg to HBeAg by Degradation of Hepatitis B Core Particles

et al. 1980

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Highly purified and homogenous hepatitis B core particles were obtained from an autopsy liver. The core particles consisted mainly of an electrophoretically single major polypeptide with a molecular weight of 20,000 daltons. When antigenic conversion from hepatitis B core antigen (HBeAg) to hepatitis B e antigen was achieved by treating these core particles by sonication or by passing them through an anti-HBc IgG-conjugated Sepharose 4B column, no appreciable changes were found in the above protein composition. The same antigenic conversion was also achieved by centrifugation of core particles in CsCl, which revealed the process of morphological disintegration accompanied by antigenic conversion. These observations may support the hypothesis that HBeAg resides on a protein conformation which consists of a polypeptide sharing HBe antigenicity.

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“…However, the presence of hepatitis B virus antigens in the glomerulus also could be a result of non specific passive trapping and not responsible for the glo merular lesion [3], Circulating immune complexes need to be very small and cationic to penetrate the basement membrane via the subepithelial space [18]. Of the hepatitis B virus associat ed antigens, HBsAg and HBeAg are large with a molecular weight in excess of two million and anionic [19,20]. HBeAg is small but also anionic [21], However, it can induce anti-HBeAb that are very cationic [22], Therefore, it is likely that a HBeAg-containing immune complex might cause hepatitis B virus MGN.…”

Section: H Epatitis B Virus Associated G Lom Erulonephrit Ismentioning

confidence: 99%

Treatment of Hepatitis B Virus Associated Glomerulonephritis with Recombinant Human Alpha Interferon

Chung

Yang²,

Kim³

et al. 1997

Am J Nephrol

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To evaluate the therapeutic effect of recombinant human α-interferon (α-IFN) on hepatitis B virus associated glomerulonephritis (HBV-GN) and the relationship between the seroconversion of viral antigens and the change of pro-teinuria, the hepatitis B viral markers and urinary protein were monitored during α-IFN treatment in 8 male adult patients who (1) were positive in serum HBsAg and HBeAg, (2) had chronic hepatitis, (3) had persistent proteinuria > 1 g/day, and (4) showed glomerulonephritis on kidney biopsy, α-IFN was given at a dose of 3 million units, subcutaneously, three times a week for 6 months. Kidney biopsy specimens showed membranoproliferative glomerulonephritis (MPGN) in 4 patients, mesangial proliferative glomerulonephritis (MesPGN) in 2, and membranous glomerulonephritis (MGN) in 2 patients. Seven of the 8 patients received a 6-month course of α-IFN therapy; 1 patient with MGN quitted therapy 2 months after the initial dose because of side effects. In 5 of the 7 patients who received a 6-month therapy, serum HBeAg disappeared, and anti-HBe appeared during the therapy. In 2 of these 5 patients, HBeAg reappeared, in 1 during α-IFN therapy and in 1 9 months after the last dose of α-IFN. The hepatitis B viral markers of the patient who received a 2-month therapy did not change. HBs antigenemia persisted in all patients. In all 4 patients with MPGN, serum HBeAg was transiently or persistently converted to negative, but the proteinuria persisted. Both patients with MesPGN showed remission of proteinuria; however, only 1 patient had seroconversion of HBeAg. In 2 patients with MGN, proteinuria persisted. In conclusion, α-IFN at the doses given was not effective in MPGN type of HBV-GN. Improvement of proteinuria was achieved in MesPGN patients without disappearance of HBs antigenemia which is the finding against the possible role of HBsAg in the pathogenesis of this type of HBV-GN.

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Biochemical and Biophysical Properties of Hepatitis B Core Particles Derived from Dane Particles and Infected Hepatocytes

Cited by 20 publications

References 13 publications

Differential Biophysical Properties of Infectious Intracellular and Secreted Hepatitis C Virus Particles

Differential Biophysical Properties of Infectious Intracellular and Secreted Hepatitis C Virus Particles

Antigenic Conversion from HBeAg to HBeAg by Degradation of Hepatitis B Core Particles

Treatment of Hepatitis B Virus Associated Glomerulonephritis with Recombinant Human Alpha Interferon

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