Search results for "Viral Core Proteins"
showing 10 items of 19 documents
Hepatitis C virus-specific T-cell-derived transforming growth factor beta is associated with slow hepatic fibrogenesis.
2011
Up to 4 million persons in the USA have chronic hepatitis C (CHC) (1). Despite a decline in overall HCV infections, the number of patients with end stage liver disease due to CHC will increase for the next 2 decades (2). Even with highly effective novel therapies, currently 30–50% of infected individuals fail treatment (3). Therefore, a better understanding of mechanisms involved in CHC-related liver disease progression could permit more efficient therapies. Adaptive effector T cells (frequently assessed by measuring production of prototypic T helper 1 cytokine IFNγ) play an important role in control of HCV infection during the acute phase (4). In CHC, effector HCV-specific T cell immune re…
Free and antibody-complexed antigen and antibody profile in apparently healthy HIV seropositive individuals and in AIDS patients.
1990
The pattern of free and antibody-complexed HIV antigen and the antibody profile were investigated retrospectively in 305 serum samples taken from 22 AIDS patients before and during the development of AIDS and from 40 apparently healthy seropositive individuals. Most AIDS patients were found positive for both free and complexed antigen and had high gp41 antibody titres but low or undetectable p24 antibody. Four different patterns of HIV antigenaemia were observed: 1) positive for both free and complexed antigen; 2) negative for free HIV antigen at first, but always positive for complexed antigen; 3) positive for free antigen without complexed antigen; and 4) negative for both free and comple…
Maturation of IgG avidity to individual rubella virus structural proteins.
2001
Background: the structural proteins of rubella virus, the capsid protein C and the envelope glycoproteins E1 and E2 were produced in lepidopteran insect cells using baculovirus expression vectors. The C-terminal ends of the corresponding proteins were fused to a polyhistidine tag for easy and gentle purification by metal ion affinity chromatography. Objectives: to investigate the maturation of natural and vaccinal IgG avidity against individual authentic and recombinant rubella virus (RV) structural proteins. Study design the analysis was carried out using a modified immunoblotting technique where the purified baculovirus-expressed proteins were compared with authentic rubella virus protein…
Hepatitis C Virus Core Protein Inhibits Tumor Suppressor Protein Promyelocytic Leukemia Function in Human Hepatoma Cells
2005
Abstract Tumor suppressor protein promyelocytic leukemia (PML) is implicated in apoptosis regulation and antiviral response. PML localizes predominantly to PML-nuclear bodies (PML-NB), nuclear macromolecular complexes regulating tumor suppressor protein p53 activity. Consistent with the function of PML in the cellular antiviral response, PML-NBs represent preferential targets in viral infections. In the case of hepatitis C virus (HCV) infection, important characteristics are nonresponsiveness to IFN therapy and development of hepatocellular carcinoma. However, the mechanisms which lead to the development of hepatocellular carcinoma are largely unknown. Here, we show that HCV core protein lo…
Upregulation of Major Histocompatibility Complex Class I on Liver Cells by Hepatitis C Virus Core Protein via p53 and TAP1 Impairs Natural Killer Cel…
2003
ABSTRACTThe mechanisms of immune evasion and the role of the early immune response in chronic infection caused by hepatitis C virus (HCV) are still unclear. Here, we present evidence for a cascade of molecular events that the virus initiates to subvert the innate immune attack. The HCV core protein induced p53-dependent gene expression of TAP1 (transporter associated with antigen processing 1) and consecutive major histocompatibility complex (MHC) class I upregulation. Moreover, in p53-deficient liver cell lines, only reconstitution with wild-type p53, but not mutated p53 lacking DNA binding capacity, showed this effect. As a consequence of increased MHC class I expression, a significantly …
Mosaic hepatitis B virus core particles presenting the complete preS sequence of the viral envelope on their surface
2004
The sequence of the preS domain of the hepatitis B virus (HBV, genotype D) envelope was inserted into the major immunodominant region (MIR) of the C-terminally truncated HBV core (HBc) protein. In Escherichia coli, the HBc–preS fusion protein was partially soluble and did not produce particles. Co-expression of the wild-type HBc as a helper protein along with the fusion protein led to the formation of mosaic HBc particles that exhibited HBc, preS1 and preS2 antigenicity. Two alternative combinations of medium- and high-copy plasmids were used for co-expression of fusion and helper proteins, in an attempt to improve mosaic particle production. However, the preS fusion content of the particle…
Interaction of wild-type and naturally occurring deleted variants of hepatitis B virus core polypeptides leads to formation of mosaic particles
2000
AbstractThe simultaneous presence of hepatitis B virus (HBV) genomes carrying wild-type (wt) and in-frame deleted variants of the HBV core gene has been identified as a typical feature of HBV-infected renal transplant patients with severe liver disease. To investigate possible interactions of wt and deleted core polypeptides a two-vector Escherichia coli expression system ensuring their concomitant synthesis has been developed. Co-expression of wt and a mutant core lacking 17 amino acid residues (77–93) within the immunodominant region led to the formation of mosaic particles, whereas the mutant alone was incapable of self-assembly.
Hepatitis B core particles as a universal display model: a structure-function basis for development
1999
AbstractBecause it exhibits a remarkable capability to accept mutational intervention and undergo correct folding and self-assembly in all viable prokaryotic and eukaryotic expression systems, hepatitis B core (HBc) protein has been favored over other proposed particulate carriers. Structurally, the unusual α-helical organization of HBc dimeric units allows introduction of foreign peptide sequences into several areas of HBc shells, including their most protruding spikes. Progress toward full resolution of the spatial structure as well as accumulation of chimeric HBc-based structures has brought closer the knowledge-based design of future vaccines, gene therapy tools and other artificial par…
Molecular Epidemiology and Immunology of Hepatitis B Virus Infection – An Update
2003
Hepatitis B virus (HBV) continues to be one of the most important viral pathogens in humans. This review provides an update on the molecular epidemiology and immunology of HBV infection. DNA sequencing has allowed replacement of the initial serotypic classification of HBV strains by a more systematic genotype system that currently consists of 7 members (genotypes A–G). More recently, sequence analysis of virus isolates from many individual patients has revealed the occurrence of certain mutational hot spots in the genome, some of which appear to correlate with the patient’s immunological and/or disease status; however, cause and effect are not always easily discernible. This holds particula…
Mosaic particles formed by wild-type hepatitis B virus core protein and its deletion variants consist of both homo- and heterodimers.
2003
AbstractCo-expression in Escherichia coli of wild-type (wt) hepatitis B virus core protein (HBc) and its naturally occurring variants with deletions at amino acid positions 77–93 or 86–93 leads to formation of mosaic particles, which consist of three dimer subunit compositions. These compositions are wt/variant HBc heterodimers and two types of homodimers, formed by wt HBc or the variant HBc themselves. Mosaic particles were found also when both HBc deletion variants 77–93 and 86–93 were co-expressed in E. coli. These findings are discussed in terms of their significance for hepatitis B virus pathogenesis and prospective use of mosaic particles in vaccine development.