Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to test components of feline leukaemia virus (FeLV) as subunit vaccines, we have constructed recombinant baculoviruses that express the FeLV envelope glycoprotein gp85 [Autographa californica nuclear polyhedrosis virus (AcNPV)-gp85] and the structural protein, gag (AcNPVgag). The gag protein is expressed and shed into the medium of infected cells as particles which have a buoyant density on sucrose gradients and appearance by electron microscopy similar to those of authentic FeLV virions. The gag precursor protein within the particles is not fully processed and appears to be a result of partial cleavage of the gag polypeptide. Insect cells that are coinfected with AcNPVgag and AcNPVgp85 shed particles that contain both the gag protein and the gp85 glycoprotein.
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PMID:Expression of feline leukaemia virus gp85 and gag proteins and assembly into virus-like particles using the baculovirus expression vector system. 132 Dec 15

To study the effects of feline leukemia virus (FeLV) on the hematopoietic microenvironment, a two-step feline long-term marrow culture (LTMC) system was developed and characterized. The adherent, stromal layer of these cultures is composed of fibroblastoid cells (50% to 80%), macrophages (10% to 30%), fat cells (10% to 20%), and large, polygonal cells that express muscle actin (1% to 2%). When fresh, enriched marrow mononuclear cells (MMNC) were added to 3-week-old irradiated stromal cultures, nonadherent erythroid progenitors (BFU-E) and granulocyte/macrophage progenitors (CFU-GM) could be detected for up to 5 and 12 weeks, respectively. LTMC stromal layers established from marrow cells from cats viremic with either a nonpathogenic strain of FeLV (FeLV-A/61E) or the anemogenic strain FeLV-C/Sarma were morphologically equivalent to uninfected LTMC stromal layers, although more than 80% of the stromal cells expressed FeLV gag protein. When FeLV-infected stromal cultures were recharged with uninfected MMNC, altered patterns of hematopoiesis were observed, compared with recharged, uninfected stromal cultures. In cultures with infected stroma, fewer nonadherent cells (NAC), nonadherent BFU-E, and nonadherent CFU-GM were detected during the first 4 to 5 weeks after recharge. In contrast, greater numbers of NAC and nonadherent CFU-GM were found from weeks 5 to 12 after recharge. When FeLV-infected stromal cultures were recharged with MMNC from a cat heterozygous for the X-chromosome-linked enzyme glucose-6-phosphate dehydrogenase (G-6-PD), the percentage of nonadherent CFU-GM expressing the domestic type G-6-PD isoenzyme remained stable over time (mean % domestic [%d], 53% +/- 3%), and was equivalent to that of nonadherent CFU-GM maintained in uninfected cultures (mean %d, 56% +/- 3%), indicating that clonal drift or clonal selection was not responsible for the enhanced maintenance of CFU-GM. Furthermore, as only 10% to 20% of recharged hematopoietic cells became infected with FeLV in vitro, it is unlikely that the altered pattern was due to progenitor infection. We hypothesize that the increase in NAC and nonadherent CFU-GM in FeLV-infected cultures resulted from enhanced growth factor production by stromal cells. The two-step LTMC system may facilitate the characterization of stromal-derived factors that affect progenitor cell engraftment and proliferation.
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PMID:Studies in feline long-term marrow culture: hematopoiesis on normal and feline leukemia virus infected stromal cells. 132 1

Marrow stromal fibroblasts (FBs) likely play an important role in the regulation of hematopoiesis within the marrow microenvironment. Infection of these cells by feline leukemia virus (FeLV) might not only contribute to the pathogenesis of FeLV-induced hematologic diseases, but could provide a reservoir for virus in the infected cat. To determine the frequency of FeLV infection among marrow FB precursor cells (fibroblast colony-forming units, CFU-F) of cats viremic with FeLV-C/Sarma and FeLV-A/61E, marrow FBs and FB cell clones were isolated and assayed for expression of FeLV gag protein. From 30% to 86% and 64% to 88% of marrow FB precursors were infected with FeLV-C/Sarma and FeLV-A/61E, respectively. CFU-F from a cat viremic with FeLV-A/61E were not affected by exposure to antibody against FeLV envelope glycoprotein gp70 and heterologous complement, whereas similarly treated hematopoietic progenitors (erythroid colony-forming units, CFU-E; erythroid burst-forming units, BFU-E; and granulocyte-macrophage colony-forming units, CFU-GM) and culture-propagated, FeLV-infected marrow FBs were effectively lysed, suggesting that infected CFU-F within the marrow microenvironment do not express a significant amount of gp70 on their cell membranes. Thus, marrow FB precursor cells appear to be a major target for FeLV in vivo. Furthermore, the low level of gp70 antigen expression on the surface of these cells in vivo may allow them to escape immune surveillance and provide a reservoir of virus during active or latent infection.
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PMID:In vivo infection of marrow stromal fibroblasts by feline leukemia virus. 132 84

The pathogenetic potential and the true extent of human T leukemia/lymphotropic virus type I (HTLV-I) and type II (HTLV-II) infection are unknown. To find out more about HTLV-I/II seroepidemiology and the risks of iatrogenic transmission, we performed a serological study, screening 4086 healthy blood donors. A surprisingly high percentage of serum reactivity to HTLV-I/II antigens was observed by commercial ELISA (2.08%) and immunoblotting (IB) (0.85%) analysis, although none of the samples satisfied the (IB) criteria for positivity based on detection of gag protein p24 and at least one env gene product, either gp46 or gp61/68. To clarify these inconclusive results, we performed polymerase chain reaction (PCR) analysis for HTLV-I and HTLV-II provirus detection in peripheral blood lymphocytes, obtained from individuals with an apparent pattern of seropositivity. The data obtained by PCR failed to reveal evidence of HTLV-I/II provirus integration in peripheral blood cells, ruling out the possibility of a viral infection in these cases, and pinpointing the limitations of both serological methods used. Our observations suggest that serological assays alone are not a reliable tool for blood donor screening of HTLV-I/II infection and raise the important question of interpreting inconclusive results.
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PMID:Absence of HTLV-I/II infection in blood donors with positive and inconclusive HTLV-I/II serology. 133 13

The ability of baicalin (7-glucuronic acid, 5,6-dihydroxyflavone), a flavonoid compound purified from the Chinese medicinal herb, Scutellaria baicalensis georgi, to inhibit human T cell leukemia virus type I (HTLV-I) was examined. Baicalin produced concentration-dependent inhibition of HTLV-I replication in productively infected T and B cells. Moreover, baicalin treatment selectively reduced the detectable levels of HTLV-I p19 gag protein in infected cells by greater than 70% at concentrations that produced insignificant effects on total cellular protein and DNA synthesis with no loss in cell viability. Resistance to HTLV-I infection and virus-mediated transformation was noted in uninfected peripheral blood lymphocytes pretreated with baicalin before cocultivation with lethally irradiated chronically infected cells. Baicalin inhibited reverse transcriptase activity in HTLV-I-infected cells as well as the activity of purified reverse transcriptase from Moloney murine leukemia virus and Rous-associated virus type 2. These results suggest that baicalin may be a potential therapeutic agent against HTLV-I-associated T cell diseases.
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PMID:Inhibition of human T cell leukemia virus by the plant flavonoid baicalin (7-glucuronic acid, 5,6-dihydroxyflavone). 137 35

We have identified and mapped the regions responsible for neutralization in the human T-cell leukemia virus type I (HTLV-I) structural proteins by using region-specific human antibodies derived from seropositive blood donors. We have obtained 18 kinds of region-specific antibody (2 in the p19 gag, 10 in the gp46 env and 6 in the gp21 env proteins) from seropositive human plasma by means of an affinity column coupled with the synthetic peptides corresponding to the antigenic regions of the HTLV-I structural proteins. These antibodies were highly specific in ELISA using synthetic peptides as an antigen. Subsequently, we examined the neutralizing activity expressed by the inhibition of virion-induced syncytium formation by region specific antibodies. Twelve of 16 antibodies derived from the env protein were able to inhibit syncytium formation induced by co-cultivation of 8C cells with HTLV-I antigen-positive T cells. The antibodies derived from the p19 gag protein and the seronegative plasma used as the control showed no significant activity. The sequences recognized by the 10 neutralizing antibodies were sites corresponding to amino acids 20 to 49, 89 to 115, 136 to 160, 175 to 199, 213 to 236, 235 to 254, 277 to 292, 332 to 352, 350 to 386, 382 to 403, 426 to 448 and 458 to 488 from the amino terminal of the env protein. These observations suggest that the neutralizing epitopes were widely distributed in the env proteins of HTLV-I.
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PMID:Neutralizing activity of human antibodies against the structural protein of human T-cell lymphotropic virus type I. 145 28

Two T-cell lines were established from peripheral blood mononuclear cells of two Moroccan patients with tropical spastic paraparesis and then named PR52 and PR144. The two cell lines showed a T lineage of activated CD4+ with high density of Tac+ (IL2 receptor). No expression of CD8 was observed. The virus particles were detected by reverse transcriptase activity and the viral antigens were also detected by immunofluorescence (IF) and Western blot. After six months of culture greater than 90% of the cells exhibited HTLVI antigen by IF. Lysate virus particles on Western blot analysis revealed p19,p24, and p53 gag protein similar to those detected in C91/PL virus particles from an adult T-cell leukemia (ATL) patient. gp46 and gp61 were also weakly detected. These two T-cell lines established will serve as substrate for further comparative studies on TSP and ATL isolates.
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PMID:Establishment of T-lymphoid cell lines from Morroccan patients with tropical spastic paraparesis. 152 May 34

We synthesized 46 sequential peptides 21 to 39 amino acids long over the structural protein of human T-cell leukemia virus type I (HTLV-I; the p19 and p24 gag protein and the gp46 and p20E env proteins) and tested their reactivities against antibodies in sera from HTLV-I healthy carriers and patients diagnosed as having human T-cell leukemia-lymphoma (ATLL) and myelopathy (HAM) by using an enzyme-linked immunosorbent assay. Of the 46 synthetic peptides, 18 peptides (2 corresponding to the p19 gag protein, 2 corresponding to the p24 gag protein, 8 corresponding to the gp46 env protein, and 6 corresponding to the p20E env protein) reacted with antibodies in the sera from HTLV-I healthy carriers. In particular, the peptides comprising amino acids 100 to 119 and 119 to 130 of the gag and 175 to 199, 213 to 236, 253 to 282, and 288 to 317 of the env proteins reacted with antibodies in sera from more than 30% of HTLV-I healthy carriers. These peptides also showed high reactivities to the antibodies in the sera from patients with ATLL and HAM. The results indicate that the predominant antigenic regions of the structural protein of HTLV-I were located at the C-terminal end of the p19 gag protein and the C-terminal half of the gp46 env protein, and the corresponding peptides proved to be useful antigens in detecting antibodies in the sera from individuals infected with HTLV-I.
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PMID:Linear antigenic regions of the structural proteins of human T-cell lymphotropic virus type I detected by enzyme-linked immunosorbent assays using synthetic peptides as antigens. 153 94

While human T-lymphotropic virus type I (HTLV-I) proviral genome is readily detected in leukemic lymphocytes from adult T-cell leukemia patients, viral antigens or viral RNA are not expressed unless these cells are cultured. To address the problem of possible restriction mechanism of HTLV-I replication, we studied the methylation state of provirus in four HTLV-I transformed cell lines. These cell lines are chronically infected with HTLV-I and carry several copies of proviruses but are characterized by different viral expression. Molecular analysis showed that in MT4 cell line, which expresses a low level of viral RNA and proteins, not only are the HTLV-I proviruses heavily methylated but methylation also involves large regions around and within the long terminal repeats. MT4 cells treatment with 5-azacytidine led to an increase in both total viral RNA and p24 gag protein expression. These findings indicate that proviral methylation is responsible for the low viral expression in MT4 cells and also suggest that this phenomenon may be relevant to HTLV-I in vivo latency.
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PMID:Human T-lymphotropic virus type I transcriptional regulation by methylation. 169 63

We have studied the process of Moloney murine leukemia virus (M-MuLV) assembly by characterization of core (gag) protein mutants and analysis of wild-type (wt) gag proteins produced by cells in the presence of the ionophore monensin. Our genetic studies involved examination of linker insertion mutants of a Gag-beta-galactosidase (Gag-beta-gal) fusion protein, GBG2051, which is incorporated into virus particles when expressed in the presence of wt viral proteins. Analysis indicated that the amino-terminal two-thirds of the gag matrix domain is essential for targeting of proteins to the plasma membrane; mutant proteins localized to the cytoplasm or were trapped on intracellular membranes. Mutations through most of the coding region of the gag capsid domain generated proteins which were released from cells in membrane vesicles but not in virions. In contrast, linker insertions into p12gag or carboxy-terminal portions of the matrix or capsid coding regions did not affect assembly of fusion proteins into virus particles. Monensin, which blocks vesicular transport, inhibited gag protein intracellular transport and release from cells. Our results suggest that a significant proportion of M-MuLV myristylated gag proteins travel via vesicles to the cell surface. Specific matrix protein polypeptide regions and myristic acid modification are both necessary for appropriate gag protein transport, while capsid protein interactions appear to mediate the final phase of virion formation.
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PMID:Transport and assembly of gag proteins into Moloney murine leukemia virus. 169 96


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