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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hepatitis delta virus (HDV) particles were produced in Huh7 human hepatoma cells by transfection with cloned hepatitis B virus (HBV) DNA and HDV cDNA. The particles were characterized by their buoyant density, the presence of encapsidated viral RNA, and their ability to infect primary cultures of chimpanzee hepatocytes. Successful infection was evidenced by the appearance of increasing amounts of intracellular HDV RNA after exposure to particles. Infection was prevented when particles were incubated with antibodies directed against synthetic peptides specific for epitopes of the pre-S1 or pre-S2 domains of the HBV envelope proteins before exposure to hepatocytes. These data demonstrate that HDV particles produced in vitro are infectious and indicate (i) that infectious particles are coated with HBV envelope proteins that contain the pre-S1 and pre-S2 regions, (ii) that epitopes of the pre-S1 and pre-S2 domains of HBV envelope proteins are exposed at the surface of HDV particles, and (iii) that antibodies directed against those epitopes have neutralizing activity against HDV.
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PMID:Production of infectious hepatitis delta virus in vitro and neutralization with antibodies directed against hepatitis B virus pre-S antigens. 130 1

To study the expression and localization of delta antigen during the replication cycle of hepatitis D virus, we cotransfected HuH-7 hepatoma cells with a hepatitis B virus expression plasmid and plasmids expressing the small or large delta antigen or the entire HDV genome. The transfected cells and culture medium were analyzed on double immunofluorescence staining for delta antigen and HBsAg, on Western blotting and on Northern-blot hybridization from 4 hr to 9 days after transfection. In cells transfected with the expression plasmid carrying the small delta antigen open reading frame, only the small delta antigen was expressed; it was localized in the nucleolus and was not released into the medium during the culture period. In cells transfected with the large delta antigen expression plasmid, the large delta antigen expressed was localized in the nucleolus at the initial stage; this was followed by relocalization in nucleoplasm. Finally, large delta antigen was released in HBsAg-enveloped particles within 1 day of transfection. In cells cotransfected with hepatitis B virus and hepatitis D virus expression plasmids, the small delta antigen was expressed 4 hr after transfection, whereas the large form was expressed 3 days after transfection. Expression of the large delta antigen coincided with the localization changes from nucleolar to mixed stage and, finally, to nucleoplasm and release of the hepatitis D virus particles. The large delta antigen appears to play a key role in relocalization of the delta antigen and packaging of the hepatitis D virus virions.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Expression and localization of the small and large delta antigens during the replication cycle of hepatitis D virus. 142 53

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

Hepatitis delta virus (HDV) has an envelope composed of large-, middle-, and small-form hepatitis B surface antigens (HBsAgs) provided by the helper hepatitis B virus (HBV). In order to examine the roles of individual HBsAgs in HDV assembly, we constructed plasmids containing each specific HBsAg gene and then cotransfected each plasmid with HDV cDNA into a permissive human hepatoma cell line (HuH-7) to examine the effects on HDV production. Results indicated that the plasmids containing only the HBsAg genes were able to complement HDV cDNA as efficiently as the plasmid containing the complete HBV genome in generating HDV-like particles. Moreover, the small-form HBsAg alone was sufficient for HDV packaging. The particles produced from the cotransfection experiments have density and protein composition characteristics similar to those of naturally occurring HDV. With the electron microscope, they were identified as 36- to 38-nm-diameter particles. It was concluded that only the HBsAgs were able to help in the assembly of HDV-like particles.
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PMID:Small-form hepatitis B surface antigen is sufficient to help in the assembly of hepatitis delta virus-like particles. 165 66

From 1973 to 1989 five patients with hepatitis delta virus having anti-hepatitis delta antibodies continuously in the serum for more than 5 years were identified among 1019 hepatitis B virus carriers who were being followed-up for more than 3 years (mean 8.9 years). Of the five patients with antibodies, three had a history of blood transfusion, in two cases the transfusion was massive, and one patient had been addicted to narcotics given intravenously 35 years before. In the remaining patient, the route of superinfection could not be determined. Hepatitis delta antigen was detected in hepatocyte nuclei of one of the three patients in whom liver biopsies were performed and there was chronic persistent hepatitis detected by an indirect immunoperoxidase technique. During the follow-up, hepatocellular carcinoma developed in one case but the clinical prognosis was favourable in the remaining four cases.
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PMID:A long-term follow-up of five patients with hepatitis delta virus in Japan. 177 9

Three viruses are responsible for posthepatitic cirrhosis: hepatitis B virus, hepatitis D (also called delta) virus and hepatitis C virus formerly known as non-A, non-B virus. Delta virus is a defective organism which can replicate only when coinfection with hepatitis B virus is present. These three viruses cause chronic active hepatitis which, after a period of 5 to 30 years, gives rise to posthepatitic cirrhosis. Chronic infections with these viruses account for more than 90 p. 100 of chronic active hepatitis in France and constitute a major cause of cirrhosis. Beside complications (hepatocellular insufficiency, portal hypertension, hepatocellular carcinoma) which are common to all types of cirrhosis irrespective of their origin, the course of posthepatitic cirrhosis is characterized by possible episodes of reactivation of chronic hepatitis and by a very high risk of hepatocellular carcinoma. Two kinds of treatment are now available: antiviral therapy (basically with interferon alpha) and liver transplantation. Antiviral therapy must, of course, be given before the stage of cirrhosis has been reached. Liver transplantation in these patients raises special problems due to recurrence of viral infection in the graft. Vaccination against hepatitis B virus, which also prevents the B-delta coinfection, must be systematic in populations at risk.
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PMID:[Post-hepatitis B, B-D and C cirrhosis]. 190 35

Hepatitis D virus and hepatitis B virus nucleic acids were detected by Northern and Southern blot hybridization in the sera and livers of 85 chronic carriers of HBsAg and anti-hepatitis D followed up for a mean of 10 yr. We identified three subsets of patients: 13 with hepatitis D virus and hepatitis B virus viremia, 53 with serum hepatitis D virus RNA, but without hepatitis B virus DNA and 19 negative for both nucleic acids. Genomic and subgenomic forms of hepatitis D virus RNA were detected only in patients with hepatitis D virus and hepatitis B virus viremia. Histological findings and disease activity at admission were comparable in the three groups of patients, but the outcome was significantly worse in patients with active replication of both viruses; two of them died of terminal liver failure and hepatocellular carcinoma developed in two; the remaining patients had an uneventful course. These results suggest that active hepatitis B virus replication represents an important previously unrecognized determinant of severe liver damage in patients with chronic hepatitis D virus infection. Since hepatitis B virus provides the means for hepatitis D virus secretion and release from infected cells, active hepatitis B virus multiplication favoring the spread of hepatitis D virus from cell to cell may increase the pathogenetic potential of the defective agent.
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PMID:Hepatitis B virus replication modulates pathogenesis of hepatitis D virus in chronic hepatitis D. 199 12

Hepatitis D virus appears to be endemic in the Middle East, but its distribution bears little relationship to that of HBV. Only in Jordan was an association between HDV-positive status and HBsAg-positive primary hepatocellular carcinoma found. Fulminant hepatitis and chronic sequelae were unusual in HDV-coinfection, while early mortality and a chronic outcome were commoner in HDV-superinfection. In established HBsAg-positive cirrhosis survival was not significantly different in the HDV-positive vs. the HDV-negative patients. In patients whose biopsies showed cirrhosis, severe necroinflammatory features were seen more often in the HDV-positive than in HDV-negative patients.
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PMID:The role of hepatitis D virus in liver disease in the Middle East. 202 Jul 22

Hepatitis may be caused by hepatitis A virus, hepatitis B virus, hepatitis C virus (classic non-A non-B viral hepatitis), hepatitis D virus (delta agent), and hepatitis E virus (epidemic non-A non-B viral hepatitis). Cytomegalovirus, Epstein-Barr virus, and herpes simplex virus may also occasionally cause hepatitis. Some forms of hepatitis carry the risks of chronic infection, cirrhosis, or hepatocellular carcinoma. Treatment options for viral hepatitis are limited and, in many cases, still under investigation. Prophylaxis is available for many forms of hepatitis and should be offered to those at risk.
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PMID:Viral hepatitis. The new ABC's. 212 Jun 86

A typical feature of an infection with the hepatitis B virus (HBV) is the development of a persistent infection manifested by a chronic carriership of hepatitis B antigen (HBsAg). There is a marked geographical variation in the frequency of the chronic HBsAg carrier state. The replication of the HBV is unique for a DNA virus and has functional characteristics of a retrovirus, i.e. replication of viral DNA through an RNA intermediate. In addition to episomal viral DNA involved in virus replication other episomal forms and integrated viral DNA have been found in infected cells. The integrated HBV DNA in liver cells is an essential factor in the development of hepatocellular carcinoma. Many epidemiological studies have made it clear that age, sex and immunological status are important factors predisposing to the development of chronic infection. Hepatitis D virus (HDV) is a distinct infectious agent but it is defective as it requires the helper function of HBV for its replication. There are two possible modes of infection, either a coinfection, i.e. simultaneous infection with HBV and HDV, or a superinfection, i.e. a chronic HBsAG carrier who becomes infected with HDV. The majority (70-90%) of all superinfections take a chronic course.
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PMID:Persistence of hepatitis B virus and establishment of delta virus infection. 226 89


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