The nucleocapsid of the hepatitis B virus: a remarkable immunogenic structure

Vanlandschoot, Peter; Cao, Tinghua; Leroux‐Roels, Geert

doi:10.1016/j.antiviral.2003.08.011

Cited by 48 publications

(35 citation statements)

References 54 publications

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“…It contains numerous epitopes for human CD4+ T cell (AA 1-20, AA 50-69 and AA 127-133), CTL (AA 18-27, AA 88-96 and AA 141-151) and B cell recognition (AA 74-89, AA 107-118 and AA 127-133) [30] . In chronic hepatitis patients, mutations have been found to preferentially locate within or flanking the dominant epitopes.…”

Section: Discussionmentioning

confidence: 99%

Hepatitis B Virus Core Protein Variations Differ in Tumor and Adjacent Nontumor Tissues from Patients with Hepatocellular Carcinoma

et al. 2011

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Objectives: To characterize the mutation pattern of a hepatitis B virus (HBV) core protein (HBcAg) derived from hepatocellular carcinoma (HCC) and adjacent nontumor tissues. Methods: HBV core gene fragments (nt. 1901–2365) were amplified from 98 HBV-related HCC tissues and 33 adjacent nontumor tissues. The deduced amino acids (AAs) of the core gene were aligned with the prototype sequences of HBV genotypes B and C. Results: In total, there were 54 positions that showed polymorphism at the deduced AA level. The mutations were predominantly located in three major (codons 83–87, 95–104 and 130–135) and three minor (codons 21–38, 59–63 and 151–155) mutation-clustering regions (MCRs). The substitution rate in MCRs was significantly higher than in mutation-devoid regions (p < 0.001). The most frequently occurring mutations in rank were codon P130T (38.8%), I97L (37.8%) and S87G (23.5%). In addition, there were 7 patients that showed internal deletions in the middle of HBcAg with sizes ranging from 34 to 59 AAs. Unexpectedly, the core genes isolated from tumor tissues had fewer mutations compared with those isolated from adjacent nontumor tissues from the same patients (p < 0.05). Conclusions: Accumulation of naturally occurring mutations in certain restricted segments of HBcAg may be related to the development of HCC.

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Section: Discussionmentioning

confidence: 99%

Hepatitis B Virus Core Protein Variations Differ in Tumor and Adjacent Nontumor Tissues from Patients with Hepatocellular Carcinoma

et al. 2011

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“…P eptides presented on MHC class I molecules are normally generated through fragmentation of proteins that have been synthesized within the cell. It is therefore remarkable that several structural proteins of viruses are quite stable in cells and nevertheless give rise to sufficient quantities of peptide to induce a CTL response (1)(2)(3). A hypothesis which reconciles this apparent contradiction is the defective ribosomal products (DRiPs) 4 hypothesis that states that CTL epitopes are not derived from properly folded proteins but from newly synthesized polypeptides that are degraded within a few minutes after their translation (4).…”

mentioning

confidence: 98%

Cross-Presentation of the Long-Lived Lymphocytic Choriomeningitis Virus Nucleoprotein Does Not Require Neosynthesis and Is Enhanced via Heat Shock Proteins

Basta

Stoessel

Basler

et al. 2005

The Journal of Immunology

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Many viral proteins that contain MHC class I-restricted peptides are long-lived, and it is elusive how they can give rise to class I epitopes. Recently, we showed that direct presentation of an epitope of the long-lived lymphocytic choriomeningitis virus nucleoprotein (LCMV-NP) required neosynthesis in accordance with the defective ribosomal products hypothesis. In this study, we report that LCMV-NP can be cross-primed in mice using either LCMV-NP-transfected human HEK293 or BALB/c-derived B8 cells as Ag donor cells. In addition, we establish that contrary to direct presentation, cross-presentation required accumulation of the mature LCMV-NP and could not be sustained by the newly synthesized LCMV-NP protein, intermediate proteasomal degradation products, or the minimal NP396 epitope. Nevertheless, NP cross-presentation was enhanced by heat shock and was blunted by inhibitors of heat shock protein 90 and gp96. We propose that cross-presentation has evolved to sustain the presentation of stable viral proteins when their neosynthesis has ceased in infected donor cells.

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“…The region between amino acids 77 to 83 of the HBc molecule constitutes the major immunodominant region (MIR) and is located at the tips of the ␣-helical hairpins that form protruding spikes (26). Therefore, we designed fusion proteins with the MIR of HBc replaced by the SP55 (PDSRESLAWQTATNP) or the SP70 (YPTFGEHKQEKDLEY) epitope of EV71, so that they can be exposed on the surfaces of the resulting chimeric HBc particles for optimal immunogenicity.…”

Section: Expression and Assembly Of Chimeric Vlps Displaying Ev71mentioning

confidence: 99%

Chimeric Virus-Like Particle Vaccines Displaying Conserved Enterovirus 71 Epitopes Elicit Protective Neutralizing Antibodies in Mice through Divergent Mechanisms

et al. 2014

J Virol

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Enterovirus 71 (EV71) is a major causative agent of hand, food, and mouth disease, which frequently occurs in young children. Since there are 11 subgenotypes (A, B1 to B5, and C1 to C5) within EV71, an EV71 vaccine capable of protecting against all of these subgenotypes is desirable. We report here the vaccine potential and protective mechanism of two chimeric virus-like particles (VLPs) presenting conserved neutralizing epitopes of EV71. We show that fusions of hepatitis B core antigen (HBc) with the SP55 or SP70 epitope of EV71, designated HBcSP55 and HBcSP70, respectively, can be rapidly generated and self-assembled into VLPs with the epitopes displayed on the surface. Immunization with the chimeric VLPs induced carrier-and epitope-specific antibody responses in mice. Anti-HBcSP55 and anti-HBcSP70 sera, but not anti-HBc sera, were able to neutralize in vitro multiple genotypes and strains of EV71. Importantly, passive immunization with anti-HBcSP55 or anti-HBcSP70 sera protected neonatal mice against lethal EV71 infections. Interestingly, anti-HBcSP70 sera could inhibit EV71 attachment to susceptible cells, whereas anti-HBcSP55 sera could not. However, both antisera were able to neutralize EV71 infection in vitro at the postattachment stage. The divergent mechanism of neutralization and protection conferred by anti-SP70 and anti-SP55 sera is in part attributed to their respective ability to bind authentic viral particles. Collectively, our study not only demonstrates that chimeric VLPs displaying the SP55 and SP70 epitopes are promising candidates for a broad-spectrum EV71 vaccine but also reveals distinct mechanisms of neutralization by the SP55-and SP70-targeted antibodies. E nterovirus 71 (EV71) is the major causative agent of hand, foot, and mouth disease, which is prevalent in the Asia-Pacific region. EV71 infection may result in severe neurological complications and even death (1-3). However, there is currently no available EV71 vaccine (4, 5).EV71 is a member of the enterovirus genus of the Picornaviridae family. It possesses a single-stranded, positive-sense RNA genome, which is encapsidated within an icosahedral capsid consisting of 60 copies of each of VP1, VP2, VP3, and VP4 subunit proteins. Based on the VP1 sequence, EV71 is categorized into three genotypes (A, B, and C), which can be further divided into eleven subgenotypes (A, B1 to B5, and C1 to C5) (reviewed in references 1 and 2). Thus, an EV71 vaccine capable of protecting against all of these subgenotypes is desirable.Increasing evidence has established that neutralizing antibodies play a key role in in vivo protection against lethal EV71 infection (reviewed in references 4 and 5). For example, Foo et al. showed that passive transfer of neutralizing antisera protects recipient mice against lethal EV71 challenge (6). Inactivated wholevirus and recombinant EV71 virus-like particles (VLPs) containing all capsid subunit proteins could elicit potent neutralizing antibodies (reviewed in references 4 and 5). Besides intact capsids, VP1 has been sh...

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The nucleocapsid of the hepatitis B virus: a remarkable immunogenic structure

Cited by 48 publications

References 54 publications

Hepatitis B Virus Core Protein Variations Differ in Tumor and Adjacent Nontumor Tissues from Patients with Hepatocellular Carcinoma

Hepatitis B Virus Core Protein Variations Differ in Tumor and Adjacent Nontumor Tissues from Patients with Hepatocellular Carcinoma

Cross-Presentation of the Long-Lived Lymphocytic Choriomeningitis Virus Nucleoprotein Does Not Require Neosynthesis and Is Enhanced via Heat Shock Proteins

Chimeric Virus-Like Particle Vaccines Displaying Conserved Enterovirus 71 Epitopes Elicit Protective Neutralizing Antibodies in Mice through Divergent Mechanisms

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