Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.7.49 (reverse transcriptase)
31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Equine protozoal myeloencephalitis (EPM) is a neurologic syndrome seen in horses from the Americas and is mainly caused by Sarcocystis neurona. Recently, a 29-kDa surface antigen from S. neurona merozoites was identified as being highly immunodominant on a Western blot. This antigen has been sequenced and cloned, and the expressed protein has been named SnSAG1. In a previous study, cell-mediated immune responses to SnSAG1 were shown to be statistically significantly reduced in horses with EPM in comparison to EPM-negative control horses. It therefore appears as though the parasite is able to induce immunosuppression towards parasite-derived antigens as parasite-specific responses are decreased. Isolated peripheral blood lymphocytes from 21 EPM (cerebrospinal fluid [CSF] Western blot)-negative horses with no clinical signs and 21 horses with clinical signs of EPM (CSF Western blot positive) were cocultured with SnSAG1 for 48 and 72 h, and the effect on cytokine production was investigated by means of reverse transcriptase PCR. Cytokines assayed include gamma interferon (IFN-gamma), tumor necrosis factor alpha, interleukin (IL)-2, IL-4, and IL-6. beta-Actin was used as the housekeeping gene. A Wilcoxon signed-rank test of the findings indicated that there was a statistically significant decrease in IFN-gamma production after 48 h in culture for samples from horses with clinical disease. There was also a statistically significant increase in IL-4 production after 72 h in culture for samples from horses with EPM. These results further support the notion that this parasite is able to subvert the immune system in horses with clinical disease.
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PMID:Cytokine gene expression in response to SnSAG1 in horses with equine protozoal myeloencephalitis. 1587 26

Chronic hepatitis B virus (HBV) infection is a major worldwide public health problem. Better therapeutics and treatment strategies are urgently needed because of ineffective clinical treatment. Our previous study showed that asialoglycoprotein receptor 1 (ASGPR1) was upregulated by HBV but downregulated by lamivudine in HepG2.2.15 cells. It has also been reported that ASGPR is a candidate receptor for HBV attachment to hepatocytes. Therefore, as a major subunit of ASGPR, ASGPR1, might be a potential target for anti-HBV drugs. To validate this hypothesis, antisense oligonucleiotides (ASODNs) were used to downregulate ASGPR1 level in HepG2.2.15 cells. By using the MFOLD web server and BLAST searches, five ASODNs theoretically targeting ASGPR1 were selected. After 72 h post-transfection, HBV-DNA level in cell medium were examined by real-time polymerase chain reaction (PCR). Hepatitis B surface antigen (HBsAg) and Hepatitis B e antigen (HBeAg) were detected using enzyme-linked immunosorbent assay (ELISA). ASGPR1 mRNA and protein level were measured by semi-quantitative reverse transcriptase (RT)-PCR and Western blot analysis respectively. The results showed that ASODN2 significantly downregulated ASGPR1 level. It also reduced HBV-DNA, HBsAg and HBeAg level in cell medium as observed with lamivudine. In contrast, the sense sequence and scrambled sequence of ASODN2 had no effect on ASGPR1 and HBV markers in HepG2.2.15 cells. This indicated that ASODN2 could specifically reduce HBV replication in vitro. Additionally, cell proliferation and apoptosis assay suggested that downregulation of ASGPR1 did not affect cell viability. We, therefore, proposed that ASODNs targeted against ASGPR1 could block HBV replication without the influence of other changes, and ASGPR1 could be targeted for anti-HBV drug development.
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PMID:Antisense oligonucleotides targeted against asialoglycoprotein receptor 1 block human hepatitis B virus replication. 1647 91

The hepatitis B virus (HBV) replicates via an error prone viral reverse transcriptase resulting in a large pool of quasispecies with mutations spread throughout the genome. During antiviral drug selection pressure (e.g., lamivudine, adefovir, or entecavir) HBV mutants are selected from the pre-existing pool of quasispecies and over time become the dominant species. Not all mutations result in replication competent virus as HBV has the added complexity of overlapping reading frames. The HBV polymerase (Pol) gene overlaps the hepatitis B surface antigen (HBsAg) in a frame-shifted manner with the result that drug-resistant mutations in the HBV Pol can directly impact on the nature of HBsAg and its function. HBV genomic databases have been established to monitor antiviral selected mutations and are useful in determining conserved residues, genotypic differences, polymorphisms, and the mutation profiles selected under different antiviral selection pressures. These HBV databases may aid in the development of new diagnostic reagents as well as the monitoring of polymerase and envelope mutations selected under different antiviral pressures. Antiviral drug resistant mutants emerge as a function of at least six factors: the viral mutation frequency, the intrinsic mutability of the antiviral target site, the selective pressure exerted by the drug, the magnitude and rate of virus replication, the overall replication fitness of the mutant, and the availability of replication space. Only a limited number of HBsAg mutations selected during antiviral treatment have been characterized and the diagnostic and public health implications of these mutations need further investigation. Clearly, improved treatment strategies are required urgently to prevent the continued selection of HBV drug-resistant mutants.
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PMID:Hepatitis B virus mutations associated with antiviral therapy. 1662 78

Hepatitis B virus (HBV) infection, which causes liver cirrhosis and hepatocellular carcinoma, remains a major health problem in Asian countries. Recent development of vaccine for prevention is reported to be successful in reducing the size of chronically infected carriers, although the standard medical therapies have not been established up to now. In this report, we encountered a patient with decompensated HBV-related cirrhosis who exhibited the dramatic improvements after antiviral therapy. The patient was a 50-year-old woman. Previous conventional medical treatments were not effective for this patient, thus this patient had been referred to our hospital. However, the administration of lamivudine, a reverse transcriptase inhibitor, for 23 months dramatically improved her liver severity. During this period, no drug resistant mutant HBV emerged, and the serum HBV-DNA level was continuously suppressed. These virological responses were also maintained even after the antiviral therapy was discontinued. Moreover, both hepatitis B surface antigen and e antigen were observed to have disappeared in this patient. The administration of lamivudine to patients with HBV-related cirrhosis, like our present case, should be considered as an initial medical therapeutic option, especially in countries where liver transplantation is not reliably available.
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PMID:Sustained clinical improvement of a patient with decompensated hepatitis B virus-related cirrhosis after treatment with lamivudine monotherapy. 1696 Mar 42

This study was carried out to investigate the putative role played by the hepatitis E virus (HEV) in acute hepatic dysfunction in paediatric patients with acute non-A-C hepatitis. We also evaluated the diagnostic value for anti-HEV immunoglobulin G (IgG) and IgM enzyme-linked immunosorbent assays relative to nested reverse transcriptase PCR (RT-PCR) for HEV RNA detection. Sixty-four children with acute hepatitis were included in the study, in addition to sixteen healthy children with matched age and sex. All studied subjects were negative for IgM antibody to hepatitis A virus, hepatitis B virus surface antigen, IgM antibody to hepatitis B virus core antigen, antibody to hepatitis C virus, and by RT-PCR for HCV RNA. HEV RNA was detected in 23.4% of patients, followed by detection of specific IgM in 17.2% and IgG in 12.5% of patients. Two cases were positive for IgG in the control group (12.5%). The sensitivity, specificity and accuracy were 26.7%, 85.7%, 71.9%, respectively, for IgM, and 26.7%, 91.8%, and 76.6%, respectively, for IgG. From this study we can conclude that HEV is a frequent virus found sporadically with acute hepatitis among paediatric patients. We cannot depend upon serology alone for diagnosis; rather, both molecular and serological methods must be applied for accurate diagnosis.
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PMID:Acute sporadic hepatitis E in children: diagnostic relevance of specific immunoglobulin M and immunoglobulin G compared with nested reverse transcriptase PCR. 1696 47

Both Secreted Protein Acidic and Rich in Cysteine (SPARC) and Hevin are multifunctional matricellular glycoproteins. Recent experimental studies suggested that Hevin and SPARC together diminish angiogenesis, but their significance in hepatocellular carcinoma (HCC) remains unclear. This study aimed to correlate SPARC and Hevin expression with angiogenesis and clinicopathological features in HCC. SPARC and Hevin protein and mRNA expression in HCC specimens were assessed by immunostaining, immunoblotting, and quantitative reverse transcriptase-polymerase chain reaction. Tumour microvessel density (MVD) was assessed by CD34 immunostaining. The role of SPARC and Hevin in HCC was further assessed in an in vivo nude mice xenograft model. Both SPARC and Hevin mRNA levels were significantly higher in tumours than in non-tumourous livers. A significant correlation between tumour SPARC and Hevin mRNA levels was found. Moreover, SPARC protein localized in the tumour sinusoidal area correlated significantly with Hevin protein localized in HCC cells. Truncated forms of SPARC and Hevin proteins were detected in clinical samples. Truncated SPARC protein localized in the tumour sinusoidal area correlated significantly with tumour MVD. On the other hand, overexpression of full-length SPARC in tumour xenografts in athymic nude mice significantly delayed tumour growth, and this delay was related to a decrease in tumour angiogenesis. Expression of Hevin protein within HCC cells was related to the presence of tumour encapsulation and the absence of hepatitis B surface antigen in clinical samples. Overexpression of Hevin in tumour xenografts also significantly delayed tumour growth. In conclusion, this study has shown that SPARC and Hevin are upregulated in HCC compared with non-tumourous liver, and that they are inter-related at both mRNA and protein levels. Moreover, both SPARC and Hevin were related to HCC angiogenesis and tumour progression.
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PMID:SPARC and Hevin expression correlate with tumour angiogenesis in hepatocellular carcinoma. 1702 19

The original hepatitis B virus (HBV) large surface antigen gene was synthesized. In order to optimize the expression of this gene in tomato plants, the tobacco pathogenesis-related protein S signal peptide was fused to the 5' end of the modified gene and the sequence encoding amino acids S, E, K, D, E, and L was placed at the 3' end. The gene encoding the modified HBV large surface antigen under the control of a fruit-specific promoter was constructed and expressed in transgenic tomato plants. The expression of the antigen from transgenic plants was confirmed by PCR and reverse transcriptase PCR. Enzyme-linked immunoassays using a monoclonal antibody directed against human serum-derived HBsAg revealed that the maximal level of HBsAg was about 0.02% of the soluble protein in transgenic tomato fruit. The amount of HBsAg in mature fruits was found to be 65- to 171-fold larger than in small or medium fruits and leaf tissues. Examination of transgenic plant samples by transmission electron microscopy proved that HBsAg had been expressed and had accumulated. The HBsAg protein was capable of assembling into capsomers and virus-like particles. To our knowledge, this is the first time the HBV large surface antigen has been expressed in plants. This work suggests the possibility of producing a new alternative vaccine for human HBV.
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PMID:Expression of the human hepatitis B virus large surface antigen gene in transgenic tomato plants. 1731 28

The co-existence of hepatitis B surface antigen (HBsAg) and anti-HBs antibodies (HBsAb) in serum of hepatitis B virus (HBV)-chronic carriers has been previously associated with HBsAg-amino acid (aa) substitutions. However, the aa pattern of HBV-reverse transcriptase (RT) and the clinical settings associated with this serological profile remain largely unknown. We studied thirteen HBsAg-positive/HBsAb-positive patients. Newly diagnosed HBsAg-positive/HBsAb-negative patients (n=51) served as controls. HBsAg/RT sequences were obtained using in-house protocols. HBsAg-positive/HBsAb-positive patients were predominantly immunosuppressed (69%). Five presented advanced liver fibrosis. HBV DNA >5.0 log(10) copies/ml was significantly more frequent than in controls. A significantly higher aa variability was observed versus controls within HBsAg major hydrophilic region (MHR), especially the a-determinant, and within RT for regions overlapping the MHR, the a-determinant, and HBsAg C terminal region where drug resistance mutations occur. Further studies are needed to determine whether this higher HBsAg/HBV-RT variability might favor dissemination of anti-HBsAb escape HBV mutants and concomitantly alter nucleos(t)ide analogs efficacy.
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PMID:Clinical and virological significance of the co-existence of HBsAg and anti-HBs antibodies in hepatitis B chronic carriers. 1757 90

Rituximab is a chimeric monoclonal antibody to the surface antigen CD20 and has provided better outcomes against CD20+ B-cell lymphomas than chemotherapy with conventional antitumor drugs alone. Treatment with rituximab poses a considerable problem, however, because of CD20- tumor transformation and subsequent disease progression. We have established a CD20- lymphoma cell line, RRBL1, from a diffuse large B-cell lymphoma with CD20- transformation from CD20+ follicular lymphoma after treatment with rituximab. RRBL1 was CD10+, CD19+, and CD20- by flow cytometry. CD20 expression was not detected by immunohistochemistry. Immunoblotting with whole RRBL1 cell lysate showed a very faint CD20 band only with longer exposures. The level of CD20 messenger RNA (mRNA) expression detected by quantitative reverse transcriptase-polymerase chain reaction analysis was almost 100 times lower than that in CD20+ lymphoma cells. When we treated RRBL1 cells with trichostatin A, an epigenetic drug that modulates histone-acetylation status, we detected dramatically increased CD20 mRNA and protein expression, suggesting that epigenetic mechanisms may explain the CD20- phenotype in RRBL1 cells. Thus, RRBL1 may be useful not only for analyses of mechanisms for the absence of CD20 expression in vitro but also for exploration of therapies against CD20- B-cell malignancies in vivo.
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PMID:Epigenetic regulation of CD20 protein expression in a novel B-cell lymphoma cell line, RRBL1, established from a patient treated repeatedly with rituximab-containing chemotherapy. 1767 67

The hepatitis B virus (HBV) polymerase and envelope genes overlap in such a way that resistance mutations to antiviral agents in the reverse transcriptase gene may affect the antigenicity of the HBV surface antigen. Mutant viruses may escape serological diagnosis using specific anti-HBV surface antigen antibodies, causing occult forms of chronic hepatitis B. Moreover, these HBV strains may evade vaccine protection, representing a public health challenge. Thus, the circulation of HBVs encoding envelope mutations selected by antiviral agents requires close monitoring.
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PMID:Hepatitis B virus escape mutants induced by antiviral therapy. 1821 41


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