Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019163 (hepatitis B)
 38,309 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Studies with heat-activated serum containing hepatitis B virus (MS2 strain) revealed 1) it was not infectious, 2) it was antigenic and 3) it was protectie. Acitve immunization with this preparation was associated with the detection of antibody to the hepatitis B surface antigen (anti-HBs) and no detectable core antibody (anti-HBc). In addition, various investigators have prepared a synthetic hepatitis B peptide vaccine, These findings indicate that it should be feasible to develop an inactivated hepatitis B vaccine by the use of purified hepatitis B surface antigen or one of its polypeptides.
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PMID:Viral hepatitis type B: prospects for active immunization. 123 80

The immune response to the X protein of human hepatitis B virus (HBV) was studied by epitope mapping by using a set of MS2-HBx fusion proteins and synthetic peptides. Antibodies in sera of patients with acute and chronic HBV infection showed a multispecific immune response. Each serum contained antibodies to a different set of epitopes, which taken together cover most of the HBx sequence. Some of the epitopes were detectable only by immunoblotting with fusion proteins; others were detectable only by an enzyme-linked immunosorbent assay (ELISA) with synthetic peptides. The carboxy-terminal half of the HBx protein was preferentially recognized by antibodies from patients with chronic hepatitis and contained a short immunodominant antigenic region with at least two major nonoverlapping epitopes. Anti-HBx antibody titers as revealed by peptide ELISAs were highest and most frequent in patients with chronic hepatitis and usually low in acutely infected patients and asymptomatic carriers. The data demonstrate a remarkable qualitative and quantitative heterogeneity of the humoral HBx immune response which can be monitored by HBx-specific peptide ELISAs. Such tests may become useful diagnostic tools.
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PMID:Mapping of B-cell epitopes of the human hepatitis B virus X protein. 169 48

To clarify the significance of the X gene of hepatitis B virus, we have tested for anti-HBx in the serum and HBxAg in the liver at different stages of the natural history of hepatitis B virus infection. Sera were screened by enzyme-linked immunosorbent assay and positive results confirmed by immunoblot. Purified recombinant MS2 Pol-HBx fusion protein was used as target for both assays. Among serial sera of patients with nonfulminant acute hepatitis, 24 of 64 patients (37.5%) were positive for anti-HBx. In fulminant cases, 15 of 36 patients (42%) had anti-HBx. In chronic hepatitis patients with high rates of hepatitis B virus replication, we found a significantly (p less than 0.01) higher prevalence of anti-HBx, 14 of 25 patients (56%), than in those with low replication, 14 of 66 patients (21%), or among asymptomatic HBsAg carrier blood donors (20 of 126 = 16%) without detectable hepatitis B virus replication (p less than 0.0001). The highest prevalence of anti-HBx was found in HBsAg carriers with cirrhosis (41 of 54 patients = 76%) and/or with hepatocellular carcinoma (18 of 33 patients = 54%). The findings suggest that anti-HBx appears as a common and early marker of hepatitis B virus infection, transient in self-limited hepatitis but persisting with progression to chronicity. In chronic hepatitis, the prevalence of anti-HBx correlated with the intensity and duration of hepatitis B virus replication but neither with the severity of the liver disease nor with malignant transformation per se.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Early and frequent detection of HBxAg and/or anti-HBx in hepatitis B virus infection. 225 44

Sera of patients with acute (AH) and chronic active hepatitis (CAH) were tested for anti-hepatitis B virus (HBV) x-protein (HBx) by immunoblotting, using recombinant MS2- and beta gal-HBx fusion proteins as substrate. Antibodies against HBx were detected in 5 out of 17 patients with AH at an early stage of infection, and in 13 out of 35 patients with CAH. Positive sera from AH patients showed a relatively weak anti-HBx reactivity when compared to sera from CAH patients. In follow up studies we tested serial serum samples from patients positive for anti-HBx. Patients with AH were observed for 3 to 6 weeks and CAH patients for up to 51 months. In general anti-HBx reactivities appeared to be stable although significant differences in apparent antibody levels were noted when sera from individual patients were compared. Our data further support an early expression of HBx-antigen in HBV-infected individuals. There was no correlation between HBe-antigen and anti-HBx in CAH.
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PMID:Antibodies to hepatitis B virus x-protein in sera of patients with acute and chronic active hepatitis. 278 68

Recombinant MS2- or beta gal fusion proteins containing parts of hepatitis B virus (HBV) HBx-, HBc-, and HBs-amino acid sequences were expressed in Escherichia coli and were used to screen 96 and 60 serum samples of HBV infected and uninfected patients, respectively, for the corresponding antibodies by immunoblotting. Antibodies against HBx were detected in 20 out of 65 sera of patients with previous resolved HBV-infection, in 3 out of 7 patients with persistent infection, and in 9 out of 24 sera of patients with acute HBV infection. The specificity of the immune reaction was confirmed by competition experiments with MS2- and beta gal-HBx fusion proteins, and by the lack of HBx antibodies in the sera of uninfected patients. Hbs and HBc antibodies were detected less frequently by immunoblotting with recombinant fusion proteins than by a commercial immunoassay. Our results indicate that HBx antibodies are induced early and frequently during HBV infection suggesting that the HBx protein is an early antigenic protein expressed in vivo.
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PMID:Frequent detection of antibodies to hepatitis B virus x-protein in acute, chronic and resolved infections. 304 38

Developments in viral hepatitis have been traced from Saul Krugman's distinction of two types, MS1 and MS2 (A and B), and Baruch S. Blumberg's discovery of Australia antigen. Hepatitis A has been grown in tissue culture, the structure of the virus is known, and the acute disease can be diagnosed. Knowledge of the molecular biology of the more complex hepatitis B virion has allowed the development of an effective vaccine and distinction of replicative and nonreplicative stages of infection. Integration, in the hepatocyte, of hepatitis B viral DNA into host DNA is the precursor of liver cancer. The infection of hepatitis B carriers with another infectious agent, delta, has added a new dimension to the problem. Other unidentified causes of hepatitis have been lumped together as non-A, non-B, and these remain to be defined and accurately diagnosed.
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PMID:Landmark perspective: Landmarks in viral hepatitis. 642 56

Recently, DNA bacteriophages (M13, lambda) have been genetically engineered to transfer genes into mammalian cells. Although efficiencies observed are still relatively low, this opens the possibility of using these viruses as a new class of transfection agents not only for fundamental research purposes but also in gene therapy protocols or in other applications like vaccination. In this respect, it has been shown that a lambda bacteriophage engineered to express the hepatitis B surface antigen in mammalian cells could elicit an immune response against this antigen in mice and rabbits without any specific targeting of the bacteriophage. These impressive results would be even more encouraging if they could be obtained with an RNA bacteriophage, as RNA vaccines are preferred over DNA vaccines for safety reasons. Up to now, RNA bacteriophages have never been engineered for gene delivery. In this paper, we have sought to determine whether such a vector could be obtained by engineering the RNA bacteriophage MS2. We show that MS2 can be produced as virus-like particles (VLPs) in Saccharomyces cerevisiae and is able to package functional heterologous mRNAs, provided that these mRNAs contain the MS2 packaging sequence. For instance, linking the MS2 packaging sequence to the human growth hormone (hGH) mRNA enabled the packaging of this particular mRNA in MS2 VLPs. Functionality in eukaryotic systems of packaged mRNAs was confirmed by showing that mRNAs purified from VLPs can be efficiently translated in vitro and in cell cultures. The high stability of MS2 could, therefore, make MS2 VLPs a very powerful carrier for RNA vaccines.
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PMID:Production in Saccharomycescerevisiae of MS2 virus-like particles packaging functional heterologous mRNAs. 1582 7

Virus-like particles (VLP) have received considerable attention for vaccine, drug delivery, gene therapy and material science applications. Although the number of unique VLP and their applications are rapidly growing, the positive impact of VLP applications is limited by the current diverse, expensive, and typically low-yielding production technologies available. These technologies, when scaled, often result in structurally and compositionally inconsistent products. We present Escherichia coli-based cell-free protein synthesis as a production technology to overcome many of the limitations of current VLP production processes. Using this technique, the MS2 bacteriophage coat protein VLP was produced at a yield 14 times the best published production yield. Also, a C-terminally truncated Hepatitis B core protein VLP was produced at similarly high yields (6 x 10(13) VLP/mL). These VLP were found to have comparable characteristics to those produced in vivo. The scalability of this technology was tested without loss in production yields. To our knowledge, this is the first time a prokaryote-based in vitro transcription/translation system has generated a virus-like particle.
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PMID:Escherichia coli-based cell-free synthesis of virus-like particles. 1802 52

Assembly of virus capsids and surface proteins must be regulated to ensure that the resulting complex is an infectious virion. In this review, we examine assembly of virus capsids, focusing on hepatitis B virus and bacteriophage MS2, and formation of glycoproteins in the alphaviruses. These systems are structurally and biochemically well-characterized and are simplest-case paradigms of self-assembly. Published data suggest that capsid and glycoprotein assembly is subject to allosteric regulation, that is regulation at the level of conformational change. The hypothesis that allostery is a common theme in viruses suggests that deregulation of capsid and glycoprotein assembly by small molecule effectors will be an attractive antiviral strategy, as has been demonstrated with hepatitis B virus.
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PMID:Virus assembly, allostery and antivirals. 2116 49

With the rapid development of molecular diagnostic techniques, there is a growing need for quality controls and standards with favorable properties to monitor the entire detection process. In this study, we describe a novel method to produce armored hepatitis B virus (HBV) and human papillomavirus (HPV) DNA for use in nucleic acid tests, which was confirmed to be stable, homogeneous, noninfectious, nuclease resistant, and safe for shipping. We demonstrated that MS2 bacteriophage could successfully package double-stranded DNA of 1.3-, 3-, 3.5-, and 6.5-kb length into viral capsids with high reassembly efficiency. This is the first application of RNA bacteriophage MS2 as a platform to encapsulate double-stranded DNA, forming virus-like particles (VLPs) which were indistinguishable from native MS2 capsids in size and morphology. Moreover, by analyzing the interaction mechanism of pac site and the MS2 coat protein (CP), we found that in addition to the recognized initiation signal TR-RNA, TR-DNA can also trigger spontaneous reassembly of CP dimers, providing a more convenient and feasible method of assembly. In conclusion, this straightforward and reliable manufacturing approach makes armored DNA an ideal control and standard for use in clinical laboratory tests and diagnostics, possessing prospects for broad application, especially providing a new platform for the production of quality controls for DNA viruses.
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PMID:A novel method to produce armored double-stranded DNA by encapsulation of MS2 viral capsids. 2598 99


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