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Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hepatitis delta virus (HDV) encodes only one protein, the hepatitis delta antigen (HDAg). Two forms of HDAg, a large (27 kDa) and a small (24 kDa) one, participate in the various steps of HDV replication. To further understand the properties of HDAg, we have constructed recombinant baculoviruses and expressed both forms of the HDAg in insect cells. The gene encoding HDAg was placed under the control of the polyhedrin promoter of Autographa Californica nuclear polyhedrosis virus (AcNPV) by homologous recombination. When Spodoptera frugiperda (Sf9) cells were infected with the recombinant viruses, both the small HDAg and the large HDAg were expressed at high levels. The HDAgs produced by the recombinants were similar in size and antigenic properties to those of the proteins produced in mammalian hepatoma cell lines. It was also localized exclusively in the nuclei. In addition, both proteins bound to HDV RNA in an in vitro assay. No difference in the RNA-binding affinity was noted between the two forms of HDAg, suggesting that the trans-dominant inhibitory activity of the large HDAg on HDV replication is not due to its competition with the small HDAg for RNA binding. Two RNA-protein complexes could be detected, suggesting either that there are at least two binding sites on the HDV RNA or that HDAg binds to HDV RNA in two multimeric forms. We have further shown that both the large and the small HDAgs are phosphoproteins, with the former having an approximately sixfold higher level of phosphorylation. Finally, it was demonstrated that the large HDAg was isoprenylated, while the small one was not. These differences in post-translational modifications are the first differences in biochemical properties demonstrated between the two forms and may explain the differential effects of the large and small HDAgs on HDV RNA replication and virus packaging.
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PMID:Hepatitis delta antigen expressed by recombinant baculoviruses: comparison of biochemical properties and post-translational modifications between the large and small forms. 152 40

The hepatitis D virus (HDV) infection plays a major role in severe liver damage caused by hepatitis. To establish the prevalence of HDV infection in haemophilic patients and patients without haemophilia, 87 patients with chronic hepatitis B virus (HBV) infection were examined for serological evidence of delta hepatitis. In addition HBV, HDV and human immunodeficiency virus type 1 (HIV) infection markers were compared to clinical and histopathological outcome of hepatitis. Out of 46 haemophiliacs 30 (65%) were anti-HD-seropositive; 10 out of 30 anti-HD-positive patients (33%) had pathological liver function tests compared to 2 out of 16 anti-HD-negative haemophiliacs (13%). The rate of HIV infection did not differ between the HDV infected and the non-HDV infected individuals with haemophilia (17/27 anti-HD-positive patients versus 12/16 anti-HD-negative patients). Two haemophilic anti-HD-positive patients underwent liver biopsy, in both cases hepatitis D antigen (HDAg) was detected in the biopsies. Only 2 out of 41 patients without haemophilia were anti-HD-positive. Both had pathological liver function tests; chronic active hepatitis and cirrhosis, respectively, were diagnosed and HDAg was found in the liver biopsies. Out of 39 anti-HD-seronegative patients without haemophilia, 26 (67%) were hepatitis B e antigen positive; in the sera of 20 patients (51%) HBV-DNA was demonstrated, but only 6 patients (15%) had pathological liver function tests. In conclusion a high seroprevalence of HDV infection was found in haemophilic patients treated with non-pasteurized commercial clotting factor concentrates. An endemic spreading of HDV infection in patients without haemophilia with chronic HBV infection could not be detected.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Correlation of hepatitis B virus, hepatitis D virus and human immunodeficiency virus type I infection markers in hepatitis B surface antigen positive haemophiliacs and patients without haemophilia with clinical and histopathological outcome of hepatitis. 153 69

Hepatitis delta virus (HDV) is a subviral satellite of hepatitis B virus (HBV). Since the RNA genome of HDV can replicate in cultured cells in the absence of HBV, it has been suggested that the only helper function of HBV is to supply HBV coat proteins in the assembly process of HDV particles. To examine the factors involved in such virion assembly, we transiently cotransfected cells with various hepadnavirus constructs and cDNAs of HDV and analyzed the particles released into the medium. We report that the HDV genomic RNA and the delta antigen can be packaged by coat proteins of either HBV or the related hepadnavirus woodchuck hepatitis virus (WHV). Among the three co-carboxy-terminal coat proteins of WHV, the smallest form was sufficient to package the HDV genome; even in the absence of HDV RNA, the delta antigen could be packaged by this WHV coat protein. Also, of the two co-amino-terminal forms of the delta antigen, only the larger form was essential for packaging.
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PMID:Assembly of hepatitis delta virus particles. 154 64

The complete RNA sequences of hepatitis delta virus (HDV) isolated at three different time points from a chronic delta hepatitis patient were determined. These time points represented three different periods of clinical flare-ups. The sequence analysis showed that these three different HDV isolates evolved at a rate ranging from 3.0 x 10(-2) to 3.0 x 10(-3) substitutions/nucleotide/year, depending on the period of infection. The evolution rates appeared to correlate with the changes of clinical pictures of hepatitis, i.e., the more drastic the change in the symptom of hepatitis was, the more nucleotide changes were detected. Except during the transition from the acute phase to chronic phase of delta hepatitis, when there was a much larger number of changes in HDV RNA sequence, the overall evolution rate of HDV RNA in the chronic phase appeared to be similar to those of other RNA viruses. Sequence relationship of these HDV RNAs suggested that acute exacerbations in chronic delta hepatitis were associated with the evolution of the persistently infected HDV, rather than resulting from new viral infections. However, some of the mutations were not cumulative, suggesting that HDV isolated at a later time was not directly evolved from the immediately previous one. Thus, HDV at any time point was a mixture of viruses with slight sequence variations, and a specific HDV RNA species was selected from this virus population under different environments. These findings indicate that HDV RNA is heterogeneous and evolves at a fast rate. The evolution rates in different parts of HDV RNA also varied. The evolution rate of HDV RNA determined here was higher than the ones determined previously from partial RNA sequences of two Japanese HDV isolates.
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PMID:Evolution of hepatitis delta virus RNA during chronic infection. 156 77

Delta hepatitis (HDV) infection can only occur in the presence of hepatitis B (HBV) infection, as HDV requires a coat of HBV surface antigen (HBsAg) for assembly of complete virus. A number of studies have examined the variation of HBV markers in serum and liver during establishment of HDV infection, but none has systematically examined the relationship between the two viruses in individual hepatocytes. Liver biopsies from five patients with HDV/HBV infection were stained for HBsAg, HBV core antigen (HBcAg) and hepatitis D (delta) antigen (HDAg). Double immunostaining was performed with a combination of indirect immunoperoxidase and alkaline phosphatase/antialkaline phosphatase techniques. HDV and HBV antigens were expressed in all five liver biopsies. Co-localization of HBsAg was seen in up to 39% of HDAg positive cells, and HBcAg in up to 8% of HDAg positive cells. HBcAg was detectable in approximately 9% of HBsAg positive cells, and HBsAg in approximately 12% of HBcAg positive cells. HDV can replicate without HBV but ultimately requires HBV to produce complete virus and subsequently infect other cells. In this study the majority of HDV positive cells did not appear to contain HBV markers. This might suggest delta virus replication without assembly, or possibly sequential production/assembly of the virus.
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PMID:Co-expression of markers for hepatitis delta and hepatitis B viruses in human liver. 157 10

The newest results on the interferon treatment of chronic viral hepatitis on the ground of controlled trials are reported. In chronic type B hepatitis about 35 percent of patients, while in chronic type C hepatitis 80 percent of patients showed good response, though in the latter disease relapse is frequent following the stop of interferon treatment. In hepatitis Delta infection further therapeutic studies are warranted. The duration of the interferon treatment in chronic viral hepatitis is still an unsolved question.
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PMID:[Chronic hepatitis treated with alpha-interferon]. 163 Aug 5

Hepatitis viruses may cause liver cancer (HCC) through an indirect mechanism inducing inflammation and cirrhosis. Only hepatitis B virus (HBV) was shown to have a direct oncogenetic potential. Hepatitis D virus (HDV) infection, superimposed on the oncogenetic background provided by chronic HBV infection, appears to provide an additional risk for HCC. Patients with florid infections from both HBV and HDV and active liver inflammation develop HCC at a significantly younger age than those infected by HBV alone or infected by hepatitis C virus (about 10 years earlier). In patients positive for serum HBV-DNA/HDV-RNA and/or IgM anti-HBc/IgM anti-HD it is mandatory to program a more frequent (thrice a year) schedule of screenings (ultrasound scan, alpha-1-phetoprotein, etc.) for prophylaxis of HCC.
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PMID:Pathobiology of chronic hepatitis virus infection and hepatocellular carcinoma (HCC). 166 Nov 97

To determine whether the abnormalities of cell-mediated immunity described in chronic D hepatitis are associated with hepatitis D virus (HDV) infection or concomitant human immunodeficiency virus (HIV) infection, serologic and tissue hepatitis B virus (HBV) and HDV markers and T lymphocyte subsets were studied in serum samples from 38 patients with chronic D hepatitis, 26 of whom had HIV infection. Patients with chronic D hepatitis and HIV infection had significantly lower peripheral blood T4:T8 ratios resulting from a significant increase in T8+ (suppressor/cytotoxic) cells, while numbers of T lymphocyte subsets were normal in cases with chronic D hepatitis only. HIV+ patients showed an increase in HBV replication (identified by hepatitis B core antigen in liver and hepatitis B e antigen and HBV DNA in serum) and in HDV replication (tissue D antigen and HDV RNA) without evidence of more active liver disease. Probably the immunologic disturbances detected in chronic D hepatitis are secondary to HIV infection, do not contribute to the pathogenesis of liver injury, and are associated with increased viral B and D replication.
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PMID:Influence of human immunodeficiency virus infection on cell-mediated immunity in chronic D hepatitis. 167 49

It has been postulated that hepatocyte injury resulting from infection with hepatitis D virus may be caused by a direct virus cytotoxicity in contrast to immune-mediated injury associated with hepatitis B virus. We have transfected HeLa and HepG2 continuous cell lines with a recombinant plasmid containing the hepatitis D antigen gene under the inducible control of the human metallothionein promoter. The addition of zinc to the cell culture medium then led to the expression of hepatitis D antigen associated with, in the short term, a significant reduction in the rate of RNA but not DNA synthesis and, in the longer term, cell death. The necrotic cells had pyknotic nuclei and shrunken eosinophilic cytoplasm; these necrotic cells resembled the apoptotic bodies seen in hepatitis D virus-related hepatitis. The level of hepatitis D antigen in individual cells that produced these changes was similar to the level of hepatitis D antigen in hepatocytes from a chimpanzee with acute hepatitis D virus infection. We conclude that the expression of hepatitis D antigen resulted in significant cytotoxic changes in these cells, providing strong support for the view that hepatitis D antigen may be specifically cytotoxic to infected hepatocytes in vivo.
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PMID:Direct evidence for cytotoxicity associated with expression of hepatitis delta virus antigen. 170 11

The presence of hepatitis delta virus genomic RNA and hepatitis delta antigen was investigated in woodchuck liver and extrahepatic tissues by in situ hybridization using synthetic radiolabeled probes, Northern-blot analysis and immunohistochemical staining for hepatitis delta antigen. Hepatitis D virus RNA and hepatitis delta antigen were detected in the nuclei of infected hepatocytes but in none of the other tissues examined. Northern-blot analysis of total cell RNA confirmed these findings and revealed a series of hepatitis D virus transcripts, including full-length genomic RNA and dimers and trimers of hepatitis D virus RNA that may represent replicative intermediates. Use of single-stranded probes showed genome-size monomers and dimers to be both of genomic and antigenomic polarity, although dimers were found to be predominantly antigenomic. These findings document the strict hepatotropism of hepatitis D virus and support the rolling-circle model of genome replication for this unique, defective RNA virus.
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PMID:An in situ hybridization, molecular biological and immunohistochemical study of hepatitis delta virus in woodchucks. 171 75


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