Severe hepatitis B is an infectious disease which has high case fatality rate and is seriously harmful to human health. Its pathogenesis is complicated. In this article are reviewed the research reports on the virus and the host factors in the course of severe hepatitis B in recent years, including the advancement of researches on viral genotypes, viral mutations, immune responses and cytokines. These data are available for exploring the pathogenesis and for developing the clinical treatment of severe hepatitis B in future.
Animals ; Cytokines ; genetics ; Hepatitis B ; genetics ; immunology ; pathology ; Hepatitis B virus ; genetics ; Humans ; Mutation

Amino Acid Sequence ; Hepatitis B Surface Antigens ; classification ; genetics ; immunology ; Hepatitis B virus ; immunology ; Mutation

Hepatitis B Core Antigens ; immunology ; Hepatitis B virus ; genetics ; immunology ; Hepatitis B, Chronic ; virology ; Humans ; T-Lymphocytes, Cytotoxic ; immunology

Bone marrow stromal antigen 2 (BST-2) is a kind of host restriction factor. Since it was discovered to be responsible for the defect in virion release of HIV-1 mutants lacking the accessory gene vpu in 2008, it was thought to mainly restrict the viruses by directly tethering viral particles at the plasma membrane. Recent reports suggest that BST-2 also can inhibit the the release of HBV particles, which are budding in the intracellular vesicles, expanding the antiviral spectrum of BST-2. Futhermore, the machanism that BST-2 used to restrict HBV release in multivesicular bodies (MVBs) is similar to that used to restrict HIV at the plasma membrane. However, HBV have evolved strategies to antagonize the antiviral action of BST-2. There are two different opinions about the antagonist. One is HBV inactivated BST-2 by HBx requiring a hepatocyte-specific environment. Another thought envelope protein HBs counteract the antiviral action of BST-2. In this review, we focus on the current advances in the anti-HBV activity of BST-2.
Animals ; Antigens, CD ; genetics ; immunology ; GPI-Linked Proteins ; genetics ; immunology ; Hepatitis B ; genetics ; immunology ; virology ; Hepatitis B virus ; genetics ; physiology ; Host-Pathogen Interactions ; Humans ; Virus Release

OBJECTIVETo investigate the presentation of a neutralization epitope-containing peptide antigen of hepatitis E virus (HEV) on chimeric virus-like particles (VLPs) of hepatitis B surface antigen (HBsAg).

METHODSThe gene fragment corresponding to amino acids (aa) 551-607 (HEnAg) of HEV capsid protein, which contains the only neutralization epitope identified to date, was fused via a synthetic glycine linker in frame with the gene of HBsAg. The resulted fusion gene was then integrated through transformation into the genome of Pichia pastoris under the control of a methanol-induced alcohol oxidase 1 (AOX1) promoter and expressed intracellularly. The expression products in the soluble cell extracts were characterized by Western blot, ELISA, CsCl density gradient analysis, and electron microscopic visualization.

RESULTSThe novel fusion protein incorporating HBsAg and the neutralization epitope-containing HEnAg was expressed successfully in Pichia pastoris with an expected molecular weight of approximately 32 kD. It was found to possess the ability to assemble into chimeric HBV/HEV VLPs with immunological physical and morphological characteristics akin to HBsAg particles. Not only did the chimeric VLPs show high activity levels in a HBsAg particle-specific ELISA but they were also strongly immunoreactive with hepatitis E (HE) positive human serum in a HEV specific ELISA, indicating that HEnAg peptide fragments were exposed on VLP surfaces and would be expected to be readily accessible by cells and molecules of the immune system. Similarity between chimeric VLPs to highly immunogenic HBsAg particles may confer good immunogenicity on surface-displayed HEnAg.

CONCLUSIONThe chimeric HBV/HEV VLPs produced in this study may have potential to be a recombinant HBV/HEV bivalent vaccine candidate.

Epitopes ; Genetic Engineering ; Hepatitis Antigens ; biosynthesis ; genetics ; immunology ; Hepatitis B Surface Antigens ; biosynthesis ; genetics ; immunology ; Hepatitis B virus ; genetics ; immunology ; Hepatitis E virus ; genetics ; immunology ; Pichia ; genetics ; Recombinant Fusion Proteins ; biosynthesis ; genetics ; isolation & purification ; Vaccines, Synthetic

Hepatitis B virus (HBV) infection has been a major global cause of morbidity and mortality. The recognition of the problem led to a worldwide effort to reduce transmission of HBV through routine infant vaccination. HBV infection is the most common cause of chronic liver diseases and hepatocellular carcinoma in Korea. After hepatitis B vaccine era, seroprevalence of hepatits B surface antigen is decreasing, particularly in children. Hepatitis B vaccine is remarkably safe and shows high immunogenicity. Universal childhood immunization with three doses of hepatitis B vaccine in the first year of life is a highly effective method for prevention and control of hepatitis B.
Hepatitis B/*epidemiology/immunology/*prevention & control ; Hepatitis B Antibodies/blood/immunology ; Hepatitis B Vaccines/immunology/therapeutic use ; Hepatitis B virus/genetics/immunology ; Humans ; Vaccination

Epitopes, T-Lymphocyte ; HLA-A2 Antigen ; immunology ; Hepatitis B Core Antigens ; genetics ; Hepatitis B virus ; genetics ; immunology ; Humans ; Mutation

BACKGROUNDTo determine the antigenicity of recombinant hepatitis E virus ORF2 (rHEV ORF2) protein expressed in Pichia pastoris (P. pastoris).

METHODSBy using the rHEV ORF2 protein from E.coli as control, an indirect ELISA was adopted to identify the sensitivity, specificity and stability of rHEV ORF2 protein from P. pastoris in detection of HEV IgM and IgG antibody in sera from patients with hepatitis E. The reactivity of the rHEV ORF2 against 5 HEV ORF2 monoclonal antibodies (McAbs) was also tested.

RESULTSThe minimum concentration of coated antigen with which HEV IgG could be detected was 12.5 ng/ml, while the highest serum dilution to detect both IgM and IgG antibodies against HEV was 1:5 120. No cross-reaction was found with sera from patients with any other types of hepatitis. The 37 degree C acceleration test showed that the rORF2 was highly stable within 12 months at 4 degrees C. The 5 HEV ORF2 McAbs showed better reaction with the rORF2 from P. pastoris, especially that 4B2, 2E2, whose reaction against the rORF2 were 125 and 25 times respectively higher than that of rORF2 from E.Coli.

CONCLUSIONThere may be more extensive conformational epitopes in the rHEV ORF2 from P. pastoris. The excellent antigenicity, sensitivity and stability suggest that it can be served as a new candidate antigen for the development of diagnostic reagents of hepatitis E.

Gene Expression ; Hepatitis Antibodies ; blood ; Hepatitis Antigens ; genetics ; immunology ; Hepatitis E ; immunology ; Hepatitis E virus ; genetics ; immunology ; Humans ; Pichia ; genetics ; metabolism ; Recombinant Proteins ; genetics ; immunology ; Viral Proteins ; genetics ; immunology

China ; epidemiology ; Hepatitis E ; epidemiology ; Hepatitis E virus ; genetics ; immunology ; Humans ; Immunoglobulin E

OBJECTIVETo search for and verify some common B cell epitopes in the core proteins of woodchuck hepatitis virus and human hepatitis B virus.

METHODSMonoclonal antibodies against both core proteins of woodchuck hepatitis virus (WHV) and human hepatitis B virus (HBV) were prepared by inoculating Balb/c mice with denatured recombination WHV and HBV core proteins. ELISA and immunoblotting assays for WHcAg and HBcAg were carried out by using these antibodies. Immunohistochemistry was carried out with liver tissue sections of both WHV-infected woodchucks and chronic HBV-infected patients. The epitopes were mapped with the mouse mAbs (6D1 and 1H4) by using a panel of 24 16mer overlapping peptides covering the entire WHcAg. The amino acid sequences of WHcAg and HBcAg were compared.

RESULTSCross-reactions were observed between mAbs (6D1 and 1H4) and WHcAg and between Mabs and HBcAg/HBcAg in ELISA and immunoblotting assay. Liver tissue sections of both WHV-infected woodchucks and chronic HBV-infected patients could be stained specifically by mAbs. The epitopes were mapped at aa1-8 (6D1) and aa125-140 (1H4) of the core proteins of both WHV and HBV by using ELISA assay. WHcAg and HBcAg share similar amino acids sequences at aa1-8 and aa125-140 respectively.

CONCLUSIONThe core proteins of woodchuck hepatitis virus and human hepatitis B virus share common linear B cell epitopes which span aa1-8 and aa125-140 respectively.

Animals ; Antibodies, Monoclonal ; biosynthesis ; B-Lymphocytes ; immunology ; Cell Line, Tumor ; Cross Reactions ; Epitopes, B-Lymphocyte ; immunology ; Hepatitis B Core Antigens ; immunology ; Hepatitis B Virus, Woodchuck ; genetics ; immunology ; Hepatitis B virus ; genetics ; immunology ; Humans ; Marmota ; Mice ; Viral Core Proteins ; immunology