Reduction and Reoxidation of Australia Antigen: Loss and Reconstitution of Particle Structure and Antigenicity

Sukeno, Noriyoshi; Shirachi, Ryoichi; Yamaguchi, Junji; Ishida, Nakao

doi:10.1128/jvi.9.1.182-183.1972

Cited by 40 publications

(8 citation statements)

References 7 publications

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“…The SVPs are compact particles with a reported density of 1.21 g/mL in caesium chloride (CsCl) compared to a density of infectious virions between 1.24 and 1.26 g/mL [23,91,92]. The compact structure of the SVPs is due to the large number of intra-and inter-molecular disulfide bonds within and between the S-domains of the individual HBsAg subunits [62,65,90,[93][94][95]. Kinetic studies demonstrated that disulfide-linked HBsAgS dimers are formed in the ER, then the immature particle precursors are transported to a post-ER, pre-Golgi compartment, which excludes the enzyme "protein disulfide isomerase" and allows the formation of HBsAgS oligomers [96].…”

Section: Biochemical Properties Of Svpsmentioning

confidence: 99%

Hepatitis B Virus (HBV) Subviral Particles as Protective Vaccines and Vaccine Platforms

Jeevan-Raj

Netter

2020

Viruses

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Hepatitis B remains one of the major global health problems more than 40 years after the identification of human hepatitis B virus (HBV) as the causative agent. A critical turning point in combating this virus was the development of a preventative vaccine composed of the HBV surface (envelope) protein (HBsAg) to reduce the risk of new infections. The isolation of HBsAg sub-viral particles (SVPs) from the blood of asymptomatic HBV carriers as antigens for the first-generation vaccines, followed by the development of recombinant HBsAg SVPs produced in yeast as the antigenic components of the second-generation vaccines, represent landmark advancements in biotechnology and medicine. The ability of the HBsAg SVPs to accept and present foreign antigenic sequences provides the basis of a chimeric particulate delivery platform, and resulted in the development of a vaccine against malaria (RTS,S/AS01, MosquirixTM), and various preclinical vaccine candidates to overcome infectious diseases for which there are no effective vaccines. Biomedical modifications of the HBsAg subunits allowed the identification of strategies to enhance the HBsAg SVP immunogenicity to build potent vaccines for preventative and possibly therapeutic applications. The review provides an overview of the formation and assembly of the HBsAg SVPs and highlights the utilization of the particles in key effective vaccines.

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Section: Biochemical Properties Of Svpsmentioning

confidence: 99%

Hepatitis B Virus (HBV) Subviral Particles as Protective Vaccines and Vaccine Platforms

Jeevan-Raj

Netter

2020

Viruses

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“…One lipoprotein particle contains ~100 HBsAg polypeptide monomers (Aggerbeck and Peterson, 1985;Ganem and Varmus, 1987;Peterson, 1987). I-IBsAg particles are unique among lipoproteins in that their structure is stabilized by extensive intermolecular disulphide crosslinking (Sukeno et al, 1972;Vyas et al, 1972;Imai et al, 1974;Peterson, 1987). It is the site of formation of these extensive crosslinks which is the subject of this paper.…”

mentioning

confidence: 94%

Hepatitis B surface antigen assembles in a post-ER, pre-Golgi compartment.

Huovila

Eder

Fuller

1992

The Journal of Cell Biology

260

221

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AbstracL Expression of hepatitis B surface antigen (HBsAg), the major envelope protein of the virus, in the absence of other viral proteins leads to its secretion as oligomers in the form of disk-like or tubular lipoprotein particles. The observation that these lipoprotein particles are heavily disulphide crosslinked is paradoxical since HBsAg assembly is classically believed to occur in the ER, and hence in the presence of high levels of protein disulphide isomerase (PDI) which should resolve these higher intermolecular crosslinks. Indeed, incubation of mature, highly disulphide crosslinked HBsAg with recombinant PDI causes the disassembly of HBsAg to dimers. We have used antibodies against resident ER proteins in double immunofluorescence studies to study the stages of the conversion of the HBsAg from individual protein subunits to the secreted, crosslinked, oligomer. We show that HBsAg is rapidly sorted to a post-ER, preGolgi compartment which excludes PDI and other major soluble resident ER proteins although it overlaps with the distribution of rab2, an established marker of an intermediate compartment. Kinetic studies showed that disulphide-linked HBsAg dimers began to form during a short (2 rain) pulse, increased in concentration to peak at 60 rain, and then decreased as the dimers were crosslinked to form higher oligomers. These higher oligomers are the latest identifiable intracellular form of HBsAg before its secretion (h/2 = 2 h). Brefeldin A treatment does not alter the localization of HBsAg in this PDI excluding compartment, however, it blocks the formation of new oligomers causing the accumulation of dimeric HBsAg. Hence this oligomerization must occur in a pre-Golgi compartment. These data support a model in which rapid dimer formation, catalyzed by PDI, occurs in the ER, and is followed by transport of dimers to a pre-Golgi compartment where the absence of PDI and a different lumenal environment allow the assembly process to be completed.NVELOPED animal viruses have been major tools in the characterization of the secretory pathway and in advancing our understanding of the mechanisms of protein sorting. Frequently, particular features of the pathways of protein traffic are exploited in the maturation pathways of different viruses so that a study of virus assembly leads to unexpected rewards in terms of an understanding of intracellular transport. This paper presents a study of the assembly of the lipoprotein particle formed by the transmembrane glycoprotein of hepatitis B virus. This particle has the unusual feature of being stabilized by extensive intermolecutax crosslinks and here we show that this reflects its assembly in an intermediate compartment between the ER and the Golgi.Hepatitis B virus (HBV) ~ is a small (440/~) DNA virus which is the type virus of the hepadnaviridae (hepatotropic DNA viruses). HBV consists of a nucleoprotein core containing a relatively small DNA genome (3,200 bp) surrounded by a protein capsid composed of the core protein, hepatitis B core antigen. The nucleocapsid i...

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“…The envelope protein of hepatitis B virus (HBV), hepatitis B surface antigen (HBsAg), is a glycosylated lipoprotein usually shed in large amounts in the serum of infected individuals, where it is found as spherical particles with a diameter of 22 nm or filaments of similar diameter [for review, see Vyas et al, 19781. Alteration of conformation by reduction or detergent treatment [Sukeno et al, 1972;Vyas et al, 1972;Dreesman et al, 19731, greatly reduces the antigenicity of HBsAg, suggesting that its immunoreactivity is largely dependent on the spatial arrangement of distinct peptide regions that collectively constitute discontinuous epitopes [Benjamin et al, 19841. Serologically, HBsAg has a dominant epitope denoted a and two sets of subtype epitopes d or y [Le Bouvier, 19711 r [Bancroft et al, 19721, which historically have been generally believed to be mutually exclusive. Combinations of these epitopes thus give the four serotypes, adw, ayw, adr, and ayr.…”

Section: Introductionmentioning

confidence: 99%

Mutations that change the immunological subtype of hepatitis b virus surface antigen and distinguish between antigenic and immunogenic determination

Ashton‐Rickardt

Murray

1989

Journal of Medical Virology

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The molecular basis of the d or y immunological subtype of hepatitis B virus (HBV) surface antigen (HBsAg) has been investigated by mutation of specific amino acid residues. When combined with substitution of serine 113 by threonine, replacement of arginine 122 by lysine or of tyrosine 134 by phenylalanine, or both of these changes, altered the antigenic subtype of HBsAg from y+d- to y+d+. These same mutations had a more dramatic effect on the subtype of antibodies induced by the antigens, a combination of all three mutations completely changing the subtype from y to d. Our study thus identifies residues in HBsAg that not only affect the subtype but discriminate between changes in antigenic and immunogenic behaviour. It also shows how the y and d subtypes may be manifest by the same molecule.

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Reduction and Reoxidation of Australia Antigen: Loss and Reconstitution of Particle Structure and Antigenicity

Abstract: Reduction of Australia antigen with dithiothreitol resulted in the loss of antigenicity and morphological integrity. Oxidation of the reduced Australia antigen reconstituted both of these characters.

Cited by 40 publications

References 7 publications

Hepatitis B Virus (HBV) Subviral Particles as Protective Vaccines and Vaccine Platforms

Hepatitis B Virus (HBV) Subviral Particles as Protective Vaccines and Vaccine Platforms

Hepatitis B surface antigen assembles in a post-ER, pre-Golgi compartment.

Mutations that change the immunological subtype of hepatitis b virus surface antigen and distinguish between antigenic and immunogenic determination

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