Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q06643 (non-Hodgkin's lymphoma)
 11,307 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To assess whether monitoring of antibodies (Ab) directed against the HIV-1 p25 core protein may be used as a predictive marker in the biological monitoring of HIV-infected patients, a study was performed on a transversal cohort of 68 CDC stage II-III, and 36 ARC and 26 AIDS stage IV patients, 37 of whom were being treated with anti-retroviral therapy. A second cohort included 56 patients followed for 3-7 years: 15 stage II-III, 11 ARC and 30 AIDS patients (opportunistic infections: 14; Kaposi's sarcoma: 11; non-Hodgkin's lymphoma: 5). p25 antigenemia and CD4+ blood lymphocyte counts were determined in parallel. Stage II-III patients usually had high and stable anti-p25 Ab levels, ARC patients exhibited more heterogeneous Ab values, while those with AIDS had very low values. No significant difference was observed in the serum anti-p25 levels of patients treated or not with anti-retroviral therapy. In patients whose CD4(+)-cell counts were going to fall below 200/mm3 and/or who were going to progress towards AIDS, the Ab levels started to decrease at a rate of > 1 log U/ml (expressed in arbitrary units/ml) per 5 years at least 2 to 4 years, respectively, before the appearance of the index symptom, despite the fact that the CD4(+)-cell count only differed significantly between progressors and non-progressors one year before the appearance of the disease.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Predictive value of the assay of serum anti-p25 antibodies in patients with human immunodeficiency virus (HIV-1) infection]. 829 42

Hepatitis C virus (HCV) core protein is a multifunctional protein. We examined whether it can interact with cellular proteins, thus contributing to viral pathogenesis. Using the HCV core protein as a bait to screen a human liver cDNA library in a yeast two-hybrid screening system, we have isolated several positive clones encoding cellular proteins that interact with the HCV core protein. Interestingly, more than half of these clones encode the cytoplasmic domain of lymphotoxin-beta receptor (LT betaR), which is a member of the tumor necrosis factor receptor family. Their binding was confirmed by in vitro glutathione S-transferase fusion protein binding assay and protein-protein blotting assay to be direct and specific. The binding sites were mapped within a 58-amino-acid region of the cytoplasmic tail of LT betaR. The binding site in the HCV core protein was localized within amino acid residues 36 to 91 from the N terminus, corresponding to the hydrophilic region of the protein. In mammalian cells, the core protein was found to be associated with the membrane-bound LT betaR. Since the LT betaR is involved in germinal center formation and developmental regulation of peripheral lymphoid organs, lymph node development, and apoptotic signaling, the binding of HCV core protein to LT betaR suggests the possibility that this viral protein has an immunomodulating function and may explain the mechanism of viral persistence and pathogenesis of HCV.
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PMID:Hepatitis C virus core protein interacts with the cytoplasmic tail of lymphotoxin-beta receptor. 899 54

Previous studies suggest that the core protein of hepatitis C virus (HCV) has a pleiotropic function in the replication cycle of the virus. To understand the role of this protein in HCV pathogenesis, we used a yeast two-hybrid protein interaction cloning system to search for cellular proteins physically interacting with the HCV core protein. One such cellular gene was isolated and characterized as the gene encoding the lymphotoxin-beta receptor (LT-betaR). In vitro binding analysis demonstrated that the HCV core protein binds to the C-terminal 98 amino acids within the intracellular domain of the LT-betaR that is involved in signal transduction, although the binding affinity of the full-length HCV core protein was weaker than that of its C-terminally truncated form. Our results also indicated that the N-terminal 40-amino-acid segment of the HCV core protein was sufficient for interaction with LT-betaR and that the core protein could form complexes with the oligomeric form of the intracellular domain of LT-betaR, which is a prerequisite for downstream signaling of this receptor. Similar to other members of the tumor necrosis factor (TNF) receptor superfamily, LT-betaR is involved in the cytotoxic effect of the signaling pathway, and thus we have elucidated the biological consequence of interaction between the HCV core protein and LT-betaR. Our results indicated that in the presence of the synergizing agent gamma interferon, the HCV core protein enhances the cytotoxic effects of recombinant forms of LT-betaR ligand in HeLa cells but not in hepatoma cells. Furthermore, this enhancement of the cytolytic activity was cytokine specific, since in the presence of cycloheximide, the expression of the HCV core protein did not elicit an increase in the cytolytic activity of TNF in both HeLa and hepatoma cells. In summary, the HCV core protein can associate with LT-betaR, and this protein-protein interaction has a modulatory effect on the signaling pathway of LT-betaR in certain cell types. Given the known roles of LT-betaR/LT-alpha1,beta2 receptor-ligand interactions in the normal development of peripheral lymphoid organs and in triggering cytolytic activity and NF-kappaB activation in certain cell types, our finding implies that the HCV core protein may aggravate these biological functions of LT-betaR, resulting in pathogenesis in HCV-infected cells.
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PMID:Direct interaction of hepatitis C virus core protein with the cellular lymphotoxin-beta receptor modulates the signal pathway of the lymphotoxin-beta receptor. 937 2

This review summarises some of the immune evasion tactics adopted by pathogens. They include the antagonism of immune function through the use of homologues of cytokine receptors, expression of viral proteins which interact with cytokine signal transduction and expression of cytokine mimics and host proteins that influence the Type I or II cytokine responses. Some of the viral defense molecules that interfere with the functions of cytokines include the EBV protein BCRF1 (viral IL-10) which blocks synthesis of cytokines such as IFN-gamma, viral IL-17 and IL-8 receptor encoded by the herpesvirus saimiri genome and chemokine receptor homologues of Epstein-Barr virus, herpesvirus saimiri and cytomegalovirus. These immunomodulatory tactics function to protect the host from the lethal inflammatory effects as well as inhibit the local inflammatory response elicited to kill the foreign pathogen. Other strategies include the alterations in cytokine expression such as demonstrated with the hepatitis B virus (HBV) core protein and terminal protein which can inhibit interferon-beta gene expression, the interactions of the hepatitis C virus core protein to lymphotoxin-beta receptor and the effects of the interferon signal transduction pathway by adenovirus EIA oncogene and HBV by reducing levels or activity of the cytosolic latent transcriptional factors (STATS). Immune evasive strategies of helminth parasites related to cytokine activities will also be briefly discussed.
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PMID:Pathogen interactions with cytokines and host defence: an overview. 965 49

Our previous study indicated that the core protein of hepatitis C virus (HCV) can associate with tumor necrosis factor receptor (TNFR)-related lymphotoxin-beta receptor (LT-betaR) and that this protein-protein interaction plays a modulatory effect on the cytolytic activity of recombinant form LT-betaR ligand (LT-alpha1beta2) but not tumor necrosis factor alpha (TNF-alpha) in certain cell types. Since both TNF-alpha/TNFR and LT-alpha1beta2/LT-betaR are also engaged in transcriptional activator NF-kappaB activation or c-Jun N-terminal kinase (JNK) activation, the biological effects of the HCV core protein on these regards were elucidated in this study. As demonstrated by the electrophoretic mobility shift assay, the expression of HCV core protein prolonged or enhanced the TNF-alpha or LT-alpha1beta2-induced NF-kappaB DNA-binding activity in HuH-7 and HeLa cells. The presence of HCV core protein in HeLa or HuH-7 cells with or without cytokine treatment also enhanced the NF-kappaB-dependent reporter plasmid activity, and this effect was more strongly seen with HuH-7 cells than with HeLa cells. Western blot analysis suggested that this modulation of the NF-kappaB activity by the HCV core protein was in part due to elevated or prolonged nuclear retention of p50 or p65 species of NF-kappaB in core protein-producing cells with or without cytokine treatment. Furthermore, the HCV core protein enhanced or prolonged the IkappaB-beta degradation triggering by TNF-alpha or LT-alpha1beta2 both in HeLa and HuH-7 cells. In contrast to that of IkappaB-beta, the increased degradation of IkappaB-alpha occurred only in LT-alpha1beta2-treated core-producing HeLa cells and not in TNF-alpha-treated cells. Therefore, the HCV core protein plays a modulatory effect on NF-kappaB activation triggering by both cytokines, though the mechanism of NF-kappaB activation, in particular the regulation of IkappaB degradation, is rather cell line and cytokine specific. Studies also suggested that the HCV core protein had no effect on TNF-alpha-stimulated JNK activity in both HeLa and HuH-7 cells. These findings, together with our previous study, strongly suggest that among three signaling pathways triggered by the TNF-alpha-related cytokines, the HCV core protein potentiates NF-kappaB activation in most cell types, which in turn may contribute to the chronically activated, persistent state of HCV-infected cells.
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PMID:Hepatitis C virus core protein enhances NF-kappaB signal pathway triggering by lymphotoxin-beta receptor ligand and tumor necrosis factor alpha. 988 79

The hepatitis C virus (HCV) core protein is a multifunctional protein. It may bind to the death domain of tumor necrosis factor receptor 1 (TNFR1) and to the cytoplasmic tail of lymphotoxin-beta receptor, implying that it may be involved in the apoptosis and anti-apoptosis signaling pathways. In vitro studies have been inconclusive regarding its ability to inhibit or enhance TNF-alpha-induced apoptosis. To address this issue, electrophoretic mobility shift assay (EMSA) and immunohistochemical studies were used to show the activation of nuclear factor kappaB (NF-kappaB) in HCV-infected liver tissues and in HCV core-transfected cells. The activation of NF-kappaB was correlated with the apoptosis assays. The results showed that NF-kappaB activation could be shown in HCV-infected livers and HCV core-transfected cells. The data of EMSA correlated with those of immunohistochemical studies, which revealed a higher frequency of NF-kappaB nuclear staining in HCV-infected than in normal livers. NF-kappaB activation conferred resistance to TNF-alpha-induced apoptosis in HCV core-transfected cells. Inhibition of NF-kappaB activation by pyrrolidine dithiocarbamate sensitized them to TNF-alpha-induced apoptosis. These findings suggest that HCV infection may cause anti-apoptosis by activation of NF-kappaB and implicate a mechanism by which HCV may evade the host's immune surveillance leading to viral persistence and possibly to hepatocarcinogenesis.
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PMID:Activation of nuclear factor kappaB in hepatitis C virus infection: implications for pathogenesis and hepatocarcinogenesis. 1070 74

Hepatitis virus, especially hepatitis C virus(HCV), is suggested to be associated with lymphomagenesis. A high prevalence(33%) of HCV among non-Hodgkin's lymphoma(NHL) patients has been reported mainly in Italy, but the prevalence is low in other countries. HCV-related NHL is varied histopathologically, including diffuse large B cell lymphoma, immunocytoma or follicular lymphoma(REAL). The HCV genotypes involved are 1b, 2a or 2c(Simmonds). Although HCV RNA + strand has been detected in lymphoma tissue in various studies, there are not many studies in which HCV RNA-strand has been detected. Recent studies have shown that BCL-2 plays an important role in lymphoproliferation by suppressing apoptosis, that HCV core protein regulates c-myc transcription and that BCL-2 and c-myc work together in lymphomagenesis. It seems difficult to provide reasonable explanations regarding these puzzling epidemiological findings and lymphomagenesis.
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PMID:[Hepatitis virus and malignant lymphoma]. 1074 Nov 25

Hepatitis C virus (HCV) is a major causative agent for chronic liver diseases leading to hepatocellular carcinoma (HCC) and has also been suggested to be a possible etiologic factor for different lymphoproliferative diseases, including mixed cryoglobulinemia (MC) and B-cell non-Hodgkin's lymphoma (NHL). To understand the roles of HCV core protein in the pathogenesis of HCV related diseases, we produced two lines of the transgenic mice (HC82310 and HC9053) that express the HCV core transgene. One of the lines, HC9053, developed malignant lymphoma (ML, follicular center cell type) with a high frequency (80%) at the ages over 20 months. Hepatocellular adenoma was also observed in this line of transgenic mouse. We demonstrated expression of HCV core protein and mRNA in the liver of transgenic mice, and also detected the core mRNA in the enlarged lymph nodes of the transgenic mice which developed ML. These results suggest that the core protein may play an important role in the development of ML, and that the HC9053 transgenic mice provide suitable models for understanding the mechanism of HCV-related lymphoproliferative diseases.
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PMID:Expression of hepatitis C virus core protein associated with malignant lymphoma in transgenic mice. 1249 92

Hepatitis C virus (HCV) core protein has been shown to deregulate cell growth and programmed cell death in hepatoma cells, but only minimal informations are available about its possible role on B-lymphoproliferative disorders (LPDs). The aim of our work was to analyze the biological activity of HCV core protein on B-cell proliferation. We established Wil2-ns and Ramos B-cell lines that stably expressed the HCV core protein. Growth curve, thymidine incorporation analysis, as well as the expression of PCNA and activated-ERKs demonstrated that HCV core protein induced an increased growth in both cell lines. Interestingly, the HCV core protein expression determined, in our model, a downregulation of DNp73 and an upregulation of DNp63, which was essential for the maintenance of viral-dependent effects on cell growth. Finally, we have identified phosphoinositide 3-kinase (PI3K) as mediator of HCV core-dependent transcriptional increase of DNp63, which in turn correlated with the increasing of lymphocyte proliferation. In primary B-lymphocytes, derived from HCV-related low-grade non-Hodgkin's lymphoma patients, consistent results were obtained. These findings provide evidence for a possible pathogenetic role played by HCV core protein in HCV-related lymphomagenesis; it could occur through the deregulation of PI3K activity, consequent activation of Akt and overexpression of DNp63.
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PMID:Involvement of PI3K in HCV-related lymphoproliferative disorders. 1765 94

HCV chronic infection leads to liver diseases and also to a wide range of extrahepatic disorders including benign, but pre-lymphomatous forms (mixed cryoglobulinemia) to frank hematological neoplasia (non-Hodgkin's lymphoma). Recent data showed the involvement of p53 superfamily members in the pathogenesis of different lymphatic malignancies. In fact, tymomas and a subset of non-Hodgkin's lymphomas (NHLs) express high levels of p63. Thus, we analyzed whether alterations in p53 superfamily gene expression are observable in B lymphocytes isolated from HCV-infected patients with and without lymphoproliferative disorders. We showed, by real-time PCR, a significant induction of DNp63 mRNAs in B lymphocytes obtained from HCV-positive low grade non-Hodgkin's lymphoma patients. Since our current understanding of HCV proteins emphasizes the ability of the HCV core protein to deregulate the expression and activity of p53-related proteins, we established different B lymphocyte cell lines (Wil2-ns, Daudi and Ramos) stably expressing HCV core protein, in order to investigate the possible involvement of the viral protein in the upregulation of DNp63 in B lymphocytes. The analysis of p63 family transcripts showed no transcriptional changes for the p63 TA isoforms, whereas an increase (>5 times) of DNp63 mRNA occurred. In all cell lines, this abnormal expression was associated with a significant increase of cell proliferation that was specifically inhibited by silencing DNp63 mRNA. These findings suggest a pathogenetic role of the HCV core in HCV-related lymphomagenesis, through the induction of DNp63's pro-proliferative effects.
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PMID:Hepatitis C virus core protein enhances B lymphocyte proliferation. 1793 28


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