Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.7.7 (DNA polymerase)
17,007 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The hepatitis B virus (HBV), the causal agent of serum hepatitis, has a diameter of 42 nm and is comprised of an outer surface coat and a 27 nm core. A unique DNA-dependent DNA polymerase is associated with the core of the virus. The core also houses a circular DNA that contains both double-stranded and single-stranded regions. In the endogenous reaction, the DNA polymerase repairs the single-stranded gaps of the viral DNA. The surface protein of the virus, called hepatitis B surface antigen, contains both lipid and carbohydrate, and is often present in particulate form in the blood of infected patients. In Asia and Africa HBV infection is associated with subsequent development of primary hepatocellular carcinoma. Although most patients recover completely from acute illness, the hepatitis B virus may cause chronic infection. Recently, a virus similar to human HBV was discovered in woodchucks. HBV has not yet been propagated in a cell culture system and the mode of replication of this unusual virus in hepatocytes is still moot. Although reliable therapy has not yet been provided, the problem of this world-wide infection has led to many interesting approaches to both vaccine production and anti-viral chemotherapy.
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PMID:The hepatitis B virus and its DNA polymerase: the prototype three-D virus. 9 Oct 92

Physicochemical studies of hepatitis B e antigen (HBeAg) revealed a clear cut difference between e1 and e2 antigen. The e1 antigen was found to have a MW of Ca 150,000 and a pI of 6.4-7.2, whereas both the MW and pI of the e2 antigen were heterogeneous depending upon the source of serum. Sera obtained from asymptomatic carriers were characterized by low titers of HBs antigen, HBc antigen and DNA polymerase and contained e2 antigen of larger molecular weight (200,000-300,000) with a narrow distribution range and a pI of 4.8 to 5.2 (type 1). On the other hand, the sera from patients in a hemodialysis unit who were HBs antigen carriers and had high titers of HBs antigen, HBc antigen and DNA polymerase contained e2 antigen of heterogeneous distribution in MW (from 300,000 to 70,000) and pI (type 2 and 3). The e2 antigen obtained from the higher MW type 3 serum had lower isoelectric points (pI 4.5 to 5.2) as was the case with e2 antigen obtained from asymptomatic carriers whereas relatively wide range of isoelectric points (pI 5.1 to 8.2) was found with the lower molecular weight e2 antigen.
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PMID:Physicochemical heterogeneity of hepatitis B e antigen detected in asymptomatic carriers and carriers in a hemodialysis unit. 9 20

Hepatitis B virus DNA made fully double stranded by a virion DNA polymerase reaction could be converted from circular to linear molecules by heating in 10 mM NaCl at 77 degrees C or in 100 mM NaCl at 90 degrees C for 15 min. Heat-generated linear hepatitis B virus DNA was reannealed to circular molecules by incubating in higher salt concentrations. The identity of the molecular forms was established by their electrophoretic mobility and appearance in electron micrographs. Recircularization was blocked by reacting linear molecules with nuclease S1 or avian myeloblastosis virus reverse transcriptase. These results suggest that the heated linear DNA had single-stranded ends with complementary nucleotide sequences. It also suggests that a discontinuity or nick is present in each strand of the circular DNA molecule after the single-stranded region is made double stranded by the virion DNA polymerase reaction. The difference in contour length by electron microscopy of circular and linear molecules spread under aqueous conditions suggested that the discontinuities in the two strands were about 270 base pairs apart. The amount of nucleotide incorporated into the ends of heat-generated linear hepatitis B virus DNA by reverse transcriptase suggested that the single-stranded ends were about 305 bases in length. This fully double-stranded linear DNA was cleaved with EcoRI or HpaI restriction endonuclease. The sum of the two fragments generated by each totaled 3,510 base pairs, 310 base pairs greater than the contour length of circular hepatitis B virus DNA which represents a third estimate of the distance between the discontinuities in the two DNA strands of circular DNA. Restriction endonuclease cleavage also indicated that the ends of heated linear DNA which correspond to the discontinuities in the two strands of the circular DNA are at unique sites in the DNA with respect to the restriction sites.
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PMID:Hepatitis B viral DNA molecules have cohesive ends. 9 58

Six patients with hepatitis B surface antigen, hepatitis B 'e' antigen positive chronic active hepatitis, and elevated hepatitis B specific DNA polymerase activity were treated sequentially with fibroblast and leucocyte interferon. Fibroblast interferon induced a fall in serum transaminase activities in all patients, whereas a consistent decline in DNA polymerase activity was observed during leucocyte interferon administration only. After treatment one patient remained persistently DNA polymerase and hepatitis B 'e' antigen negative, whereas relapse to initial values occurred in others. Side effects included severe but reversible granulocytopenia, and chills responding to promethazine treatment. The differential biologies with their non-identity in in vitro studies.
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PMID:Differential effects of fibroblast and leucocyte interferon in HBsAg positive chronic active hepatitis. 11 47

Hepatitis B virus-like particles (including DANE particles) with DNA polymerase activity but negative for HBs Ag have been identified in NON-A, NON-B hepatitis sera positive for HC Ag. Although specifically associated with the particles, HC Ag is not a surface antigen of the hepatitis C virus identified here for the first time. The relationship of this agent with HBV seems obvious, and deserves further study.
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PMID:[Identification of a virus similar to hepatitis B virus in non-A non-B hepatitis]. 12 Jul 82

Resulting directly from the discovery of virus-related antigens, rapid progress has marked the last decade of viral hepatitis research. The hepatitis B virion has been tentatively identified as a DNA virus with an endogenous DNA polymerase, and new serological markers for type B hepatitis have been discovered. Hepatitis A antigen has been identified on a virus-like particle thought to be the hepatitis A virion. Progressively more sophisticated assays for hepatitis antigens and antibodies have been applied to the study of viral hepatitis epidemiology and biochemical-biophysical characterization of the agents. Most recently, knowledge learned from such studies has been exploited to develop a prototype non-infectious but immunogenic hepatitis B vaccine using hepatitis B surface antigen (HBsAg) purified in large quantities from chronic HBsAg carriers. Especially exciting is the prospect, suggested by serological studies of viral hepatitis, that hepatitis viruses besides hepatitis A and B viruses will be identified.
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PMID:Recent advances in the identification of hepatitis viruses. 19 74

DNA of hepatitis B virus (HBV) of hepatitis B surface antigen (HBsAg) subtype adw2 made fully double stranded by the virion DNA polymerase and radiolabeled either by the virion DNA polymerase reaction or by nick-translation with 32P-labeled deoxynucleoside triphosphates was used to establish a map of restriction endonuclease cleavage sites by the method double and triple enzyme digestion and to determine the relative positions of several unique physical features of this DNA. The five restriction sites for enzyme HincII, the two sites each for BamHI, Ava I, and Bgl II, and the single sites for EcoRI, Pst I, Hpa I, and Taq I were positioned relative to each other. Within this map, the single-stranded region in HBV DNA has been localized and the locations of nicks in each strand (a and b) have been determined with respect to restriction sites on the circular map. Comparison of restriction endonuclease cleavage patterns of DNAs of HBV of HBsAg subtypes adw2, ayw3, and adrq+ revealed consistent differences among subtypes and occasional differences within subtypes.
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PMID:Restriction endonuclease cleavage map and location of unique features of the DNA of hepatitis B virus, subtype adw2. 29 95

Although several studies have been done to analyze the peptides of purified 22-nm HbsAg particles, no information has been published about the peptides of the core of the Dane particle which bears the other hepatitis B viral antigen. HbcAg. Dane particles and Dane particle cores (produced by NP-40 treatment of Dane particles) were purified by equilibrium centrifugation in CsCl density gradients. Two populations of Dane particles were observed at densities 1.27 and 1.24 g/ml, respectively. The higher buoyant density Dane particles yielded exclusively cores of buoyant density 1.38 g/ml in CsCl, and the lower buoyant density Dane particles yielded two kinds of cores with buoyant densities of 1.38 and 1.325 g/ml, respectively. Only the higher density Dane particles and cores manifested endogenously primed DNA polymerase activity. The peptides of density 1.38 g/ml Dane particle cores purified by equilibrium CsCl density gradient centrifugation and HBcAg particles from HBV infected chimpanzee liver purified in the same way were analyzed by SDS-polyacrylamide gel electrophoresis. Both kinds of particles were found to consistently contain 3 Coomassie blue staining peptides with approximate molecular weights of 19,000, 70,000 and 80,000 daltons (designated P-19, P-70 and P-80 respectively). In addition, the HBcAg particles from infected liver regularly yielded a protein component with molecular weight greater than 200,000 daltons. This component was occasionally present in electrophoresis runs of core peptides from only one of two patients. Its irregular appearance after gel electrophoresis suggests it may have been an aggregate not completely dissociated under the conditions used. The lower density core component consistently contained P-19, P-70, and P-80, and infrequently additional minor peptides of uncertain origin. The irregular occurrence of the minor peptides in varying amounts suggests they were not intrinsic core proteins.
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PMID:The proteins of hepatitis B Dane particle cores. 30 49

A 23 year old woman with chronic active hepatitis documented by liver biopsy demonstrated persistent hepatitis B surface antigen, hepatitis B virus specific DNA polymerase hepatitis B core antigen (HBcAg), for approximately one year. The number of circulating T lymphocytes that rosetted with sheep erythrocytes was decreased, and a rosette-inhibitory factor was present in her peripheral blood. Interferon treatment (1 X 10(6) U/day intramuscularly for 82 days) resulted in a decrease of HBsAg and disappearance of HBcAg, (HBeAg) and specific DNA polymerase. In addition, the number of T lymphocytes increased to normal, and the rosette-inhibitory factor disappeared from the circulation. These findings suggest that the effect of interferon in chronic active hepatitis is mediated in part through its action on the immune system.
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PMID:Fibroblast interferon treatment of a patient with chronic active hepatitis. Increased number of circulating T lymphocytes and elimination of rosette-inhibitory factor. 31 5

Hepatitis B immune globulin (HBIG) and immune serum globulin (ISG) were examined in a randomized, double-blind trial to assess their relative efficacies in preventing type B hepatitis after needle-stick exposure to hepatitis B surface antigen (HBsAG)-positive donors. Clinical hepatitis developed in 1.4% of HBIG and in 5.9% of ISG recipients (P = 0.016), and seroconversion (anti-HBs) occurred in 5.6% and 20.7% of them respectively (P less than 0.001). Mild and transient side-effects were noted in 3.0% of ISG and in 3.2% of HBIG recipients. Available donor sera were examined for DNA polymerase (DNAP) and e antigen and antibody (HBeAg; anti-HBE). Both DNAP and HBeAg showed a highly statistically significant correlation with the infectivity of HBsAg-positive donors. Hepatitis B immune globulin remained significantly superior to ISG in preventing type B hepatitis even when the analysis was confined to these two high-risk subgroups. The efficacy of ISG in preventing type B hepatitis cannot be ascertained because a true placebo group was not included.
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PMID:Type B hepatitis after needle-stick exposure: prevention with hepatitis B immune globulin. Final report of the Veterans Administration Cooperative Study. 34 78


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