Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019163 (hepatitis B)
 38,309 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Antibodies to polymerized human albumin (poly-HSA) could not be detected by using sensitive methods (enzyme-linked immunosorbent assay and radioimmunoprecipitation) in sera from chronic carriers of hepatitis B surface antigen (HBsAg) or in serial bleedings from one chimpanzee infected with type A hepatitis virus and one infected with non-A, non-B hepatitis virus. By a solid-phase radioimmunoassay, receptor sites for poly-HSA could be detected on HBsAg particles from sera containing either hepatitis B "e" antigen (HBeAg) or anti-HBe. Blocking experiments showed that monomeric HSA did not bind to this receptor. In general, the HBsAg particles from sera with HBeAg had more poly-HSA receptor sites or relatively more particles carrying this receptor compared with HBsAg from sera with anti-HBe. Microtiter plates coated with poly-HSA bound HBsAg from sera containing HBeAg with greater efficiency than did anti-HBs coupled to a solid phase (Ausria II beads), whereas with sera positive for anti-HBe, the two assays were equally sensitive. Decreased ability of HBsAg to bind to poly-HSA was seen in some sera which had been stored for a few years at 4 degrees C, whereas the binding to anti-HBs was unaffected. It is possible that polymers of albumin on the surface of hepatocytes could function as receptors for hepatitis B virus.
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PMID:Sites that bind polymerized albumin on hepatitis B surface antigen particles: detection by radioimmunoassay. 50 Jan 99

It is generally accepted that the hepatitis B virus is not cytopathic and that liver cell damage in chronic HBV infection is dependent on the host's immune response directed at viral and self-antigens on the surface of infected hepatocytes. In recent years there have been some advances in the understanding of both the viral antigen display on hepatocytes and the resultant host response. Using fluoresceinated polyclonal and monoclonal antibodies to HBV antigens, HBcAg has been identified as the major viral product expressed on the surface of liver cells isolated from patients with chronic HBV infection. In these patients, both T and non-T cells from peripheral blood have been shown to be cytotoxic to autologous hepatocytes. Blocking studies using polyclonal anti-HBs and anti-HBc antibodies indicate that HBcAg, but not HBsAg, is an important target antigen for T-cell attack, and this has recently been confirmed using monoclonal reagents. The non-T cell cytotoxicity appears to be directed at auto-antigens in a liver membrane lipoprotein complex (LSP), probably through an antibody-dependent (ADCC) mechanism. T-cell bypass mechanisms could be responsible for the production of autoantibodies to these normal membrane components. Both these mechanisms of cytolysis are found, most often, in patients with active viral replication in the HBeAg-positive phase of chronic HBV infection. This is presumably because hepatocytes containing free HBV-DNA and expressing HBcAg on their surface will be most susceptible to T-cell attack, while those with integrated HBV-DNA only express HBsAg and are relatively protected.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Immunopathological mechanisms of liver cell injury in chronic hepatitis B virus infection. 349 75

Hepatitis D virus (delta agent) markers were present in 111 (36%) of 308 intravenous drug abusers who were positive for hepatitis B surface antigen (HBsAg), 52 of these having hepatitis D virus antigenaemia. IgM antibody to hepatitis B core antigen (anti-HBc IgM) was present in 92 out of 95 subjects tested, indicating that hepatitis D virus and hepatitis B virus infections had been acquired simultaneously. Hepatitis D virus markers were present in three out of four patients with fulminant hepatitis, and in 80 of 223 (36%) with mild or moderate hepatitis compared with four of 29 (14%) of those who were asymptomatic. These proportional differences were significant (p less than 0.001). Hepatitis D virus markers were present in twice as many patients positive for anti-HBc IgM requiring admission to hospital with acute hepatitis compared with outpatients attending a drug treatment centre. Tests on one patient showed complete disappearance of HBsAg, but hepatitis D antigen (HDAg or delta antigen) and hepatitis B e antigen (HBeAg) were still present in serum samples. All five patients with chronic active hepatitis had hepatitis D antibody (anti-HD) compared with seven of 24 (29%) with chronic persistent hepatitis (p = 0.008). Blocking anti-HD persisted for long periods after simultaneous infections with hepatitis B virus and hepatitis D virus but at lower titres than in patients with chronic liver disease.
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PMID:Increased severity and morbidity of acute hepatitis in drug abusers with simultaneously acquired hepatitis B and hepatitis D virus infections. 392 1

Binding activity of antibodies against polymerized human serum albumin (pHSA) was measured in the serum of 348 patients with various hepatic and non-hepatic diseases and in the serum of 108 control persons. The methods used were passive hemagglutination (PH) with antigen loaded human erythrocytes and radial immunodiffusion (ID). In the PH-method only HBsAg-positive sera reacted. Blocking experiments with pHSA, polymerized bovine serum albumin (pBSA) and monomeric human serum albumin (mHSA) showed, that the PH-method measures HBsAG associated receptors for pHSA. In HBeAG-positive cases titers were significantly higher than in anti-HBe-positive sera. Using the ID-method it could be shown, that 40% of sera of patients with liver diseases (n = 272), 37% of patients with LED (n = 27), 72% of patients with rheumatoid arthritis (n = 32), 6% of patients with glomerulonephritis (n = 17) and 2% of normal persons (n = 108) reacted. These sera reacted in the immunodiffusion assay with pHSA and pBSA but not with mHSA. Autoantibodies against non species specific determinants of pHSA which are not specific for liver diseases and possibly due to disturbed immunoregulation can be demonstrated by immunodiffusion. They may possibly be modulators of the pHSA mediated binding of hepatitis B-virus to hepatocytes.
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PMID:[Detection of autoantibodies to polymerized human serum albumin]. 643 69

Hepatitis B virus (HBV) X protein (HBx) plays an essential role in development of HBV-associated hepatocellular carcinoma (HCC). Recently, we reported that HBx induces Fas Ligand (FasL) expression, which may help HCC cells to evade host-immune surveillance. The aim of this study was to investigate the role of HBx in expression of Nur77, an orphan nuclear receptor implicated in the upregulation of FasL. When Chang X-34 expressing HBx under the control of a doxycycline-inducible promoter was examined, induction of Nur77 was observed following HBx expression. Blocking of Nur77 function by introduction of an antisense or a dominant negative mutant Nur77 significantly inhibited the induction of FasL, indicating that Nur77 plays critical roles in FasL expression. Further, a high-level expression of transcripts and DNA binding of Nur77 were observed in the HBV-integrated cell lines established from HCC patients that express HBx. These results suggested that Nur77 may contribute to leading the HBx-induced Fas/FasL signaling pathway which eliminates invading Fas-expressing lymphocytes.
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PMID:Hepatitis B virus X protein induced expression of the Nur77 gene. 1170 33

It is well-documented that alcohol drinking together with hepatitis viral infection accelerates liver injury; however the underlying mechanisms remain unknown. In this paper, we demonstrated that primary hepatocytes from transgenic mice overexpressing hepatitis B virus X protein (HBX) were more susceptible to ethanol- and TNF-alpha-induced apoptotic killing. Compared to normal control mouse hepatocytes, ethanol and/or TNF-alpha treatment led to a significant increase in reactive oxygen species, mitochondrial permeability transition, cytochrome C release, caspase-3 activity, and poly (ADP-ribose) polymerase degradation in hepatocytes from HBX transgenic mice. Blocking caspase-3 activity antagonized ethanol- and TNF-alpha-induced apoptosis in primary hepatocytes from HBX transgenic mice. Taken together, our findings suggest that HBX sensitizes primary mouse hepatocytes to ethanol- and TNF-alpha-induced apoptosis by a caspase-3-dependent mechanism, which may partly explain the synergistic effects of alcohol consumption and hepatitis B virus infection on liver injury.
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PMID:Hepatitis B virus X protein sensitizes primary mouse hepatocytes to ethanol- and TNF-alpha-induced apoptosis by a caspase-3-dependent mechanism. 1621 10

Most human immunodeficiency virus type 1 (HIV-1) strains require either the CXCR4 or CCR5 chemokine receptor to efficiently enter cells. Blocking viral binding to these coreceptors is an attractive therapeutic target. Currently, several coreceptor antagonists are being evaluated in clinical trials that require characterization of coreceptor tropism for enrollment. In this report, we describe the development of an automated and accurate procedure for determining HIV-1 coreceptor tropism (Trofile) and its validation for routine laboratory testing. HIV-1 pseudoviruses are generated using full-length env genes derived from patient virus populations. Coreceptor tropism is determined by measuring the abilities of these pseudovirus populations to efficiently infect CD4+/U87 cells expressing either the CXCR4 or CCR5 coreceptor. Viruses exclusively and efficiently infecting CXCR4+/CD4+/U87 cells are designated X4-tropic. Conversely, viruses exclusively and efficiently infecting CCR5+/CD4+/U87 cells are designated R5-tropic. Viruses capable of infecting both CXCR4+/CD4+/U87 and CCR5+/CD4+/U87 cells are designated dual/mixed-tropic. Assay accuracy and reproducibility were established by evaluating the tropisms of well-characterized viruses and the variability among replicate results from samples tested repeatedly. The viral subtype, hepatitis B virus or hepatitis C virus coinfection, and the plasma viral load did not affect assay performance. Minority subpopulations with alternate tropisms were reliably detected when present at 5 to 10%. The plasma viral load above which samples can be amplified efficiently in the Trofile assay is 1,000 copies per ml of plasma. Trofile has been automated for high-throughput use; it can be used to identify patients most likely to benefit from treatment regimens that include a coreceptor inhibitor and to monitor patients on treatment for the emergence of resistant virus populations that switch coreceptor tropism.
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PMID:Development and characterization of a novel single-cycle recombinant-virus assay to determine human immunodeficiency virus type 1 coreceptor tropism. 1711 63

The preS2 domain is the minimal functional unit of transcription activators that is encoded by the Hepatitis B virus (HBV) surface (S) gene. It is present in more than one-third of the HBV-integrates in HBV induced hepatocarcinoma (HCC). To further understand the functional role of PreS2 in hepatocytes, a PreS2 expression plasmid, pcS2, was constructed and stably transfected into HepG2 cells. We conducted growth curve and colony-forming assays to study the impact of PreS2 expression on cell proliferation. Cells transfected with PreS2 proliferated more rapidly and formed colonies in soft agar. PreS2 expressing cells also induced upregulation of human telomerase reverse transcriptase (hTERT) and telomerase activation by RT-PCR and the modified TRAP assay. Blocking expression of hTERT with antisense oligonuleotide reversed the growth rate in cells stably transfected with PreS2. Our data suggest that PreS2 may increase the malignant transformation of human HCC cell line HepG2 by upregulating hTERT and inducing telomerase activation.
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PMID:In vitro transfection of the hepatitis B virus PreS2 gene into the human hepatocarcinoma cell line HepG2 induces upregulation of human telomerase reverse transcriptase. 1730 51

Hepatitis B x antigen (HBxAg) is a trans-activating protein that contributes to liver cancer, in part, by altering the expression of cellular genes. However, few natural effectors of HBxAg have been identified. Hence, HBxAg positive and negative HepG2 cells were prepared and analyzed by PCR select cDNA subtraction. The results identified elevated vascular endothelial growth factor receptor-3 short form splice variant (VEGFR-3(S)) expression in HBxAg positive compared to negative cells. Normally, VEGFR-3 activates Akt signaling in lymphatic endothelial cells, resulting in lymphangiogenesis. In contrast, the results here show that the expression of VEGFR-3(S) is up-regulated in >75% of HBxAg positive hepatocellular carcinoma (HCC) nodules. VEGFR-3(S) up-regulation correlates with the expression of HBxAg, is associated with decreased survival in tumor bearing patients, and when over-expressed in HepG2 cells, strongly stimulated cell growth in culture, in soft agar, and accelerated tumor formation in a ligand independent manner. VEGFR-3(S) siRNA partially blocked the ability of HBxAg to promote hepatocellular growth. In conclusion, HBxAg may short circuit VEGFR-3(S) signaling in liver cancer. Blocking VEGFR-3(S) signaling may be effective in preventing tumor development and/or prolonging survival in tumor bearing patients.
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PMID:Hepatitis B x antigen up-regulates vascular endothelial growth factor receptor 3 in hepatocarcinogenesis. 1753 24

Hepatitis B virus (HBV) infection afflicts over 350 million people worldwide and is a leading cause of hepatitis, cirrhosis and hepatocellular carcinoma. HBV replicates noncytopathically in hepatocytes, and most of the hepatic injury is caused by the immune response to the virus. While most studies focused on the adaptive immune response, the role of the innate immune response, especially the complement activation, in HBV infection remains obscure. To identify proteins that are involved in the pathogenesis of HBV infection, we carried out gene microarray analysis to compare the gene expression profile of HBV transgenic BALB/c mice with that of control mice. CD59 mRNA, which encodes an important complement regulatory protein (CRP) expressed on cell surface, was found to be significantly downregulated in HBV transgenic liver, a result that was further confirmed by RT-PCR and real-time PCR. To explore the relationship between CD59 and HBV infection, we examined the effect of HBV on CD59 expression and complement-dependent cytolysis in two hepatocyte cell lines. We found that HBV could significantly downregulate CD59 expression and sensitize cells to complement-dependent lysis. Blocking CD59 function using a CD59-specific antibody greatly diminished the HBV effect. Similar CD59 downregulation was also observed in the livers of patients with chronic HBV infection. These results demonstrate that HBV can sensitize hepatocytes to complement-dependent cytotoxicity (CDC) through downregulating CD59, which may lead to the activation of complement system and cause liver inflammation.
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PMID:Hepatitis B virus sensitizes hepatocytes to complement-dependent cytotoxicity through downregulating CD59. 1980 10


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