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)

A hepatoblastoma cell line transfected with hepatitis B virus (HBV) DNA (Hep G2.2.15) was used to investigate the effects of interferons (IFNs) on HBV replication and hepatocellular gene expression. IFN-alpha 2b or -beta inhibited HBV replication transiently. In parallel, there was a decrease in the amount of HBV mRNA. Hepatitis B surface antigen and early antigen secretion were not influenced; however, their intracellular levels diminished during treatment. The cellular 2',5'-oligoadenylate synthetase activity was increased 9- to 18-fold during treatment of cells with IFN-gamma, -alpha, or -beta. The number of IFN-alpha and -beta receptors was down-regulated, while the number of IFN-gamma receptors remained constant. The expression of major histocompatibility complex class I antigens was stimulated by addition of IFN-alpha or -beta. These data show that both IFN-alpha and -beta can effectively inhibit HBV replication and induce a cellular IFN response in Hep G2.2.15 cells similar to that seen in humans.
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PMID:Type I interferons inhibit hepatitis B virus replication and induce hepatocellular gene expression in cultured liver cells. 132 10

The activities of 2',5'-oligoadenylate synthetase (2-5AS) in spleen and liver extracts obtained from mice treated with recombinant mouse interferon-beta (rMuIFN-beta) were investigated. The levels of the enzyme activity increased significantly in both spleen and liver extracts for 72 hours after the treatment with rMuIFN-beta (5 X 10(4)IU). The levels of the enzyme activity in spleen extracts correlated well with those in liver extracts. Therefore it is suggested that the assay of 2-5AS activity in peripheral blood mononuclear cells (PBMC) of patients infected with hepatitis B virus (HBV) is useful for monitoring the antiviral state of liver during IFN therapy. The activities of 2-5AS in PBMC obtained from patients with chronic hepatitis B (CHB) were significantly higher than those of healthy controls, resulting from the endogenous IFNs detected in the patients with CHB. Furthermore, the enzyme activities of PBMC in the patients with CHB increased significantly during IFN therapy as compared with IFN-untreated patients. This increase in the enzyme levels during IFN therapy correlated well with the decrease of DNA-polymerase (DNA-P) activities associated with HBV. These results indicate that the assay of 2-5AS detected in PBMC from the patients is valuable to determine the optimal IFN therapy for CHB.
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PMID:[2',5'-oligoadenylate synthetase activity in peripheral blood mononuclear cells obtained from patients with chronic hepatitis B during interferon therapy]. 222 95

Alkaline ribonuclease (RNase; EC 3.1.27.5) activities and 2',5'-oligoadenylate synthetase (2-5 AS; no EC no. assigned) activities in serum were measured in nine patients with hepatitis B e antigen-positive chronic hepatitis B before, during, and after treatment with recombinant human interferon alpha-2b for four weeks at daily doses ranging from 3 to 10 mega-units. Alkaline RNase activities in serum significantly increased from 65.8 +/- 9.5 units/L (mean +/- SD) to 84.3 +/- 11.9 units/L after the first week of therapy (P less than 0.001). (One unit of RNase activity is defined as that increasing the absorbance at 260 nm by 1.0 in 1 min). This increase persisted during and until two weeks after the end of the therapy, at which time the mean RNase activity in serum was still significantly increased (70.8 +/- 9.4 units/L, P less than 0.01). Before therapy, phosphocellulose chromatography of RNase showed five active peaks of enzyme activity, which were similar to that observed even when RNase activity increased immediately after therapy. There was a close correlation between RNase activities and the logarithm of 2-5 AS activities, measured simultaneously in each patient. We conclude that recombinant alpha-interferon therapy increases RNase activities in serum, associated with the increased 2-5 AS activities.
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PMID:Effects of recombinant leukocyte interferon on ribonuclease activities in serum in chronic hepatitis B. 235 34

We measured 2',5'-oligoadenylate synthetase activities in serum and peripheral blood mononuclear cells from 10 patients with chronic hepatitis B who were being treated with interferon so as to determine whether 2',5'-oligoadenylate synthetase activity in serum reflected 2',5'-oligoadenylate synthetase activity in peripheral blood mononuclear cells, and whether it could be used to monitor interferon treatment. Pretreatment values of 2',5'-oligoadenylate synthetase activity in patients' serum and peripheral blood mononuclear cells were not statistically different from values from control subjects. When interferon was administered, serum levels of 2',5'-oligoadenylate synthetase began to rise within 3 hr, reached peak values at 12 hr and then declined. The levels of 2',5'-oligoadenylate synthetase activity both in serum and peripheral blood mononuclear cells increased substantially during interferon treatment, ranging 2- to 50-fold greater than initial levels. The levels of 2',5'-oligoadenylate synthetase in serum correlated closely with levels in peripheral blood mononuclear cells. In addition, when the levels of 2',5'-oligoadenylate synthetase rose during interferon administration, serum hepatitis B virus DNA polymerase values fell, and, in some cases, DNA polymerase rose again when 2',5'-oligoadenylate synthetase fell after discontinuation of interferon. These findings suggest that 2',5'-oligoadenylate synthetase activity in serum accurately reflects the antiviral effect of interferon and could be used to monitor interferon treatment.
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PMID:Serum 2',5'-oligoadenylate synthetase activity during interferon treatment of chronic hepatitis B. 245 34

We measured 2',5'-oligoadenylate synthetase activity in peripheral blood mononuclear cells and serum of 14 HBsAg- and HBeAg-positive patients with chronic hepatitis B with or without acute exacerbation. Elevated levels of 2',5'-oligoadenylate synthetase in peripheral blood mononuclear cells and serum were found in seven chronic hepatitis B patients with acute exacerbation, whereas in the remaining seven chronic hepatitis B patients without acute exacerbation, both levels were similar to those of normal subjects despite active hepatitis B virus multiplication. 2',5'-Oligoadenylate synthetase levels in peripheral blood mononuclear cells and serum, which were not statistically different from those of normal subjects prior to acute exacerbation, increased during acute exacerbation from 3- to 23-fold over initial levels following elevations in ALT activity. 2',5'-Oligoadenylate synthetase levels fluctuated over a normal range while ALT levels were elevated, and they returned to a baseline with ALT normalization. This suggests that the in vivo interferon system may be activated during acute exacerbation, and that this activation may not be a result of hepatitis B virus multiplication alone, but also of a host-immune response to hepatitis B virus multiplication. Three patients were treated with interferon during acute exacerbation. All three had elevated levels of 2',5'-oligoadenylate synthetase in peripheral blood mononuclear cells and serum just before treatment. 2',5'-Oligoadenylate synthetase levels increased only 1.1- to 2.2-fold over initial levels during treatment, with none of the patients clearing HBeAg during and after treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Elevated levels of 2',5'-oligoadenylate synthetase activity in peripheral blood mononuclear cells and serum during acute exacerbation of chronic hepatitis B. 246 93

Two years or more after 35 patients (29 men and six women) with chronic hepatitis B were treated by interferon, we studied relationships of age, ALT activity, activity of serum DNA polymerase associated with the hepatitis B virus, serum levels of hepatitis B e antigen and activity of 2',5'-oligoadenylate synthetase in peripheral blood mononuclear cells when treatment started in comparison with treatment results. Seventeen patients were given human lymphoblastoid interferon-alpha; the other 18 patients were given interferon-beta. We measured the activity of 2',5'-oligoadenylate synthetase in these mononuclear cells and found the rate of increase in vivo and in vitro; the correlation between the two was r = 0.68. This enzyme activity in the patients who became negative for DNA polymerase after interferon treatment increased more both in vivo and in vitro than in patients who did not became negative. Also, both the in vivo and in vitro activity increased more in patients who became negative for the e antigen after interferon therapy than in those who remained positive. In the first group, interferon was considered to be effective; in the second, ineffective. Of the patients who became negative, some developed e antibodies and some did not; the increase in this enzyme activity in the two groups was not significantly different. The increase in the activity of 2',5'-oligoadenylate synthetase activity could be used to predict the results of interferon treatment and is an index that can be used before treatment to predict the response.
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PMID:Relationship of the effects of interferon on chronic hepatitis B and the induction of 2',5'-oligoadenylate synthetase. 247 40

Recombinant human granulocyte-macrophage colony-stimulating factor therapy significantly reduces serum hepatitis B virus DNA levels, associated with increased 2',5'-oligoadenylate synthetase activity in cultured mononuclear cells of patients with chronic hepatitis B. To assess changes in immune function during therapy of chronic hepatitis B patients, spontaneous and mitogen-induced production of tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6, interferon-alpha and interferon-gamma were measured-along with serum levels of soluble CD4, soluble CD8, soluble interleukin-2 receptor and beta 2-microglobulin-before, during and after a 6-wk course of granulocyte-macrophage colony-stimulating factor in nine patients with chronic hepatitis B. Treatment statistically enhanced spontaneous production of tumor necrosis factor-alpha (p < 0.05) and interleukin-1 beta (p < 0.02). Furthermore, spontaneous interleukin-6 production correlated negatively with hepatitis B virus DNA levels (p < 0.03), and spontaneous interleukin-1 beta production correlated positively with 2',5'-oligoadenylate synthetase activity (p < 0.0005). In addition, statistically significant increases were found during therapy in serum levels of soluble interleukin-2 receptor (p < 0.01), soluble CD4 (p < 0.01) and beta 2-microglobulin (p < 0.05). Levels of soluble interleukin-2 receptor and soluble CD4 correlated negatively with levels of hepatitis B virus DNA (p < 0.05), and levels of soluble interleukin-2 receptor and beta 2-microglobulin correlated positively with 2',5'-oligoadenylate synthetase activity (p < 0.003 and p < 0.02, respectively). Thus recombinant human granulocyte-macrophage colony-stimulating factor administration may induce reductions in hepatitis B virus DNA levels, perhaps by altering the immune status and increasing cytokine production.
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PMID:Changes in cytokine production during therapy with granulocyte-macrophage colony-stimulating factor in patients with chronic hepatitis B. 792 47

The human MxA protein is a new specific marker for type I interferon activity both in vitro and in vivo. In the study presented here, this interferon-induced marker, as well as the 2',5'-oligoadenylate synthetases, was measured in circulating mononuclear cells from 21 patients with acute hepatitis A, 20 patients with acute hepatitis B and 14 patients with acute hepatitis C for determination of the activation of the interferon system in these viral diseases. In acute hepatitis A a strong expression (10 of 10 patients) of the MxA protein and the 2',5'-oligoadenylate synthetase activity in peripheral-blood mononuclear cells was observed during the first 2 wk after onset of clinical symptoms. In this period the MxA protein concentrations reached levels similar to those measured in patients treated with up to 5 x 10(6) IU interferon-alpha three times a week. Beyond wk 3, in eight of eight patients with hepatitis A no increased MxA protein levels were found. In contrast, peripheral-blood mononuclear cells from patients with acute hepatitis B contained either no measurable MxA protein or only slightly higher levels of the MxA protein, as did those of most patients (12 of 14) with acute hepatitis C. The MxA protein levels of both hepatitis B and C patients were significantly lower (p < 0.05) than those found in hepatitis A patients. Furthermore, sera from 6 of 10 patients with hepatitis A, but none of 10 patients with acute hepatitis B and C, contained measurable MxA protein. This serum MxA protein may originate from interferon-exposed and subsequently damaged liver cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Strong transient expression of the type I interferon-induced MxA protein in hepatitis A but not in acute hepatitis B and C. 813 57

The effects of tumor necrosis factor-alpha and/or interferon-gamma on the replication of hepatitis B virus were examined using HB611 cells. These cells were derived from human hepatoblastoma cells, Huh6, by integrating hepatitis B virus DNA, and produce hepatitis B virus continuously. Each of the cytokines inhibited hepatitis B virus replication in the cells assessed as the amount of episomal hepatitis B virus DNA, without a decrease in cell viability. When the two cytokines were administered together, the inhibitory effect became greater. Incubation of the cells with 1,000 U/ml tumor necrosis factor-alpha decreased HBV DNA replicative intermediates by 55%, and that with 1,000 U/ml interferon-gamma decreased these by 51%. Furthermore, incubation with 1,000 U/ml tumor necrosis factor-alpha and 1,000 U/ml interferon-gamma in combination decreased HBV DNA replicative intermediates by 71%. In contrast, the amount of hepatitis B virus RNA and secretion of hepatitis B e antigen were not apparently reduced by the cytokines, and 2',5'-oligoadenylate synthetase activity was not detected in the supernatant. These results suggest that tumor necrosis factor-alpha and interferon-gamma inhibit hepatitis B virus replication by blocking some step in reverse transcription and that the 2',5'-oligoadenylate synthetase is not involved in the mechanism underlying the inhibition by these two cytokines.
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PMID:Tumor necrosis factor-alpha and interferon-gamma inhibit synergistically viral replication in hepatitis B virus-replicating cells. 855 Dec 80

Hepatitis B, C, and D viruses can infect liver cells and in some individuals establish a chronic phase of infection. Presently, relatively little information is available on the antiviral mechanisms in liver cells. Because no good in vitro model infection systems for hepatitis viruses are available, we have used influenza A, Sendai, and vesicular stomatitis (VSV) viruses to characterize interferon (IFN) responses and IFN-induced antiviral mechanisms in human hepatoma cell lines. HepG2 or HuH7 cells did not show any detectable IFN-alpha/beta production in response to influenza A or Sendai virus infections. Treatment of cells with IFN-alpha resulted in upregulation of IFN-alpha-inducible Mx, 2',5'-oligoadenylate synthetase (OAS) and HLA class I gene expression but only with exceptionally high levels of IFN-alpha (>/=100 IU/ml). Accordingly, high pretreatment levels of IFN-alpha, 1000 IU/ml for influenza A and VSV and 100 IU/ml for Sendai virus, were required before any detectable antiviral activity against these viruses was seen. IFN-gamma had some antiviral effect against influenza A virus but appeared to be ineffective against VSV and Sendai virus. IFN-gamma upregulated HLA class I protein expression, whereas Mx or OAS expression levels were not increased. There was a modest upregulation of HLA class I expression during Sendai virus infection, whereas influenza A virus infection resulted, after an initial weak upregulation, in a clear decrease in HLA class I expression at late times of infection. The results suggest that hepatoma cells may have intrinsically poor ability to produce and respond to type I IFNs, which may contribute to their inability to efficiently resist viral infections.
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PMID:Impaired antiviral response in human hepatoma cells. 1054 9


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