Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.7 (DNA polymerase)
 17,007 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The discovery of Australian antigen (HBsAg) has led to an increasing deal of knowledges about the virus of type B hepatitis (HBV); several markers of HBV have been detected and are becoming disposable for clinical and epidemiological purposes. The HBsAg is carried by 3 types of particulate structures discovered by electron microscopy as small spherical particles having diameter around 22 nm, long filaments and spherical particles having an overall diameter of the 42 nm (Dane-particle) with an electron-dense core. Dane-particle core contains circular double-stranded DNA molecules and an enzyme, the DNA polymerase. At present, Dane-particle is thought to represent the HBV, having properties consistent with those of a complete virus. Four antigen/antibody systems related to viral type B hepatitis have been discovered; they have been designated with the following nomenclature: HBsAg/anti-HBs, HBcAg/anti-HBc, HBeAg/anti-HBe, epilon antigen/anti epilson. The availability of the HBV markers for clinical purposes will permit a better understanding of the sequence of the biological reactions as well as of the clinical and epidemiological features concerning this viral infection: incubation period, acute disease, resolution, chronic carrier state, actively or passively immunized subject, persistent or subsided infectivity, prognosis.
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PMID:[Markers of type B viral hepatitis]. 38 66

In acute cases of hepatitis, DNA polymerase activity was found 2 to 3 times more frequently than positive radioimmunoassay. For each case the DNA polymerase reactivity was shown to be associated with hepatitis B antigens. Inhibitors to this DNA polymerase, with properties of IgM and IgG antibody, were found in 13 of 34 cases of acute hepatitis but only in 1 case out of 22 of cirrhosis. During the course of the acute disease these antibodies were detected 3 times more frequently than those to HBs antigen; the two types of antibodies were almost always found separately in different patients, those to DNA polymerase were apparently transient and developed earlier since they were found as early as 3 days after the clinical onset and no later than the 6th week following the onset.
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PMID:Comparison of DNA polymerase and radioimmune assays for the detection of hepatitis B antigens and antibodies. 120 57

Hepatitis B virus (HBV) replicates its DNA genome through reverse transcription of an RNA intermediate. The lack of proofreading capacity of the viral DNA polymerase results in a high mutation rate of HBV genome. Under the selective pressure created by the nucleos(t)ide analogue (NA) antiviral drugs, viruses with resistance mutations are selected. However, the replication fitness of NA-resistant mutants is markedly reduced compared to wild-type. Compensatory mutations in HBV polymerase, which restore the viral replication capacity, have been reported to arise under continuous treatment with lamivudine (LMV). We have previously identified a highly replicative LMV-resistant HBV isolate from a chronic hepatitis B patient experiencing acute disease exacerbation. Besides the common YMDD drug-resistant mutations, this isolate possesses multiple additional mutations in polymerase and core regions. The transcomplementation assay demonstrated that the enhanced viral replication is due to the mutations of core protein. Further mutagenesis study revealed that the P5T mutation of core protein plays an important role in the enhanced viral replication through increasing the levels of capsid formation and pregenomic RNA encapsidation. However, the LMV-resistant virus harboring compensatory core mutations remains sensitive to capsid assembly modulators (CpAMs). Taken together, our study suggests that the enhanced HBV nucleocapsid formation resulting from core mutations represents an important viral strategy to surmount the antiviral drug pressure and contribute to viral pathogenesis, and CpAMs hold promise for developing the combinational antiviral therapy for hepatitis B.
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PMID:Naturally occurring core protein mutations compensate for the reduced replication fitness of a lamivudine-resistant HBV isolate. 3090 4