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)

Circulating 'free' non-enveloped Hepatitis C virus (HCV) core protein has been demonstrated in HCV-infected patients, and HCV subgenomes with deletions of the envelope proteins have been previously identified. Initial studies from our laboratory, previously published, indicated that expression of HCV core in insect cells can direct the formation of capsid-like particles lacking the envelope glycoproteins. These protein nanospheres, morphologically similar to natural capsids, were shown to be taken up by human hepatic cells and to produce cell-signalling events. To follow the intracellular fate of these particles we fused the core protein to eGFP. We demonstrate that the chimeric proteins core(173)-eGFP, eGFP-core(191) and eGFP-core(173) can be efficiently expressed, self-assembled, and form fluorescent non-enveloped capsid-like particles. By using confocal microscopy and FACS analysis, we provide evidence that the fluorescent nanospheres can not only enter human hepatic cells - the main target of HCV - but also human immune cells such as T and B lymphocytes, as well as human myeloid leukaemia cells differentiated along the monocyte/macrophage-like pathway. The fluorescent particles might thus be used to trace the intracellular trafficking of naked HCV capsids as showed by live microscopy and to further understand their biological significance.
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PMID:Green fluorescent protein - Tagged HCV non-enveloped capsid like particles: development of a new tool for tracking HCV core uptake. 1940 Dec 14

A mass spectrometry (MS) approach was used to analyze viral core proteins of the murine leukemia virus (MuLV)-based gene delivery vector. The retroviral particles produced by traditional methods were concentrated and purified by ultracentrifugation and spin column for matrix-assisted laser desorption ionization (MALDI) and electrospray ionization (ESI) MS. MALDI application detected all core MuLV proteins, partial degradation of p10, phosphorylation of p12, as well as the previously unknown formation of a polymeric supramolecular complex between p15 and p30 core proteins. ESI provided information on the post-translational modifications of MuLV core proteins. Data suggest myristoylation of p15 and oxidation of methionine residues in both p12 and p30, whereas cysteine residues in p10, p15 and p30 were not oxidized. The current study demonstrates that MALDI and ESI are efficient tools for viral core protein analysis and can be used as analytical tools in virology and biotechnology of gene delivery vectors.
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PMID:Mass spectrometry of murine leukemia virus core proteins. 2069 Dec 7

Scar tissue at sites of traumatic injury in the adult central nervous system presents a combined physical and molecular impediment to axon regeneration. Of multiple known central nervous system scar associated axon growth inhibitors, semaphorin 3A has been shown to be strongly expressed by invading leptomeningeal fibroblasts. We have previously demonstrated that infusion of the small leucine-rich proteoglycan decorin results in major suppression of several growth inhibitory chondroitin sulphate proteoglycans and growth of adult sensory axons across acute spinal cord injuries. Furthermore, decorin treatment of leptomeningeal fibroblasts significantly increases their ability to support neurite growth of co-cultured adult dorsal root ganglion neurons. In the present study we show that decorin has the ability to suppress semaphorin 3A expression within adult rat cerebral cortex scar tissue and in primary leptomeningeal fibroblasts in vitro. Infusion of decorin core protein for eight days resulted in a significant reduction of semaphorin 3A messenger RNA expression within injury sites compared with saline-treated control animals. Both in situ hybridization and immunostaining confirmed that semaphorin 3A messenger RNA expression and protein levels are significantly reduced in decorin-treated animals. Similarly, decorin treatment decreased the expression of semaphorin 3A messenger RNA in cultured rat leptomeningeal fibroblasts compared with untreated cells. Mechanistic studies revealed that decorin-mediated suppression of semaphorin 3A critically depends on erythroblastic leukaemia viral oncogene homologue B4 and signal transducer and activator of transcription 3 function. Collectively, our studies show that in addition to suppressing the levels of inhibitory chondroitin sulphate proteoglycans, decorin has the ability to suppress semaphorin 3A in the injured central nervous system. Our findings provide further evidence for the use of decorin as a potential therapy for promoting axonal growth and repair in the injured adult mammalian brain and spinal cord.
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PMID:Decorin, erythroblastic leukaemia viral oncogene homologue B4 and signal transducer and activator of transcription 3 regulation of semaphorin 3A in central nervous system scar tissue. 2111 66

Retroviral vectors derived from the murine leukemia virus (MuLV) are widely used as the starting material in the development of vectors for gene therapy and critical in answering questions relating to viral pathogenesis. The p30 capsid (CA) is the major viral core protein and an internal group antigen in MuLV. In this study, an enzyme-linked immunosorbent assay (ELISA) was developed for quantitation of MuLV infectious particles with p30 CA core antigen protein. The ELISA was developed using several goat-polyclonal serum against MuLV p30 generated by the NCI as primary antibody and a rat-monoclonal antibody to CA available from ATCC. The MuLV p30 CA antigen was standardized against recombinant MuLV p30 CA expressed from bacteria. The assay is sensitive, accurate and linear within a defined concentration range of CA. Comparison with different MuLV quantitative methods including reporter gene transfer, reverse transcriptase activity assay, and viral RNA quantitative PCR, showed this ELISA protocol to be highly quantifiable within defined ranges, which can be correlated with infectious viral titer.
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PMID:Development of an enzyme-linked immunosorbent assay based on the murine leukemia virus p30 capsid protein. 2381 Aug 54

Feline leukemia virus (FeLV) is an oncogenic retrovirus of cats. Immunoassays for the p27 core protein of FeLV aid in the detection of FeLV infections. Commercial microtiter-plate ELISAs have rapid protocols and visual result interpretation, limiting their usefulness in high-throughput situations. The purpose of our study was to validate the PetChek FeLV 15 ELISA, which is designed for the reference laboratory, and incorporates sequential, orthogonal screening and confirmatory protocols. A cutoff for the screening assay was established with 100% accuracy using 309 feline samples (244 negative, 65 positive) defined by the combined results of FeLV PCR and an independent reference p27 antigen ELISA. Precision of the screening assay was measured using a panel of 3 samples (negative, low-positive, and high-positive). The intra-assay coefficient of variation (CV) was 3.9-7.9%; the inter-assay CV was 6.0-8.6%. For the confirmatory assay, the intra-assay CV was 3.0-4.7%, and the inter-assay CV was 7.4-9.7%. The analytical sensitivity for p27 antigen was 3.7 ng/mL for inactivated whole FeLV and 1.2 ng/mL for purified recombinant FeLV p27. Analytical specificity was demonstrated based on the absence of cross-reactivity to related retroviruses. No interference was observed for samples containing added bilirubin, hemoglobin, or lipids. Based on these results, the new high-throughput design of the PetChek FeLV 15 ELISA makes it suitable for use in reference laboratory settings and maintains overall analytical performance.
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PMID:Analytical validation of a reference laboratory ELISA for the detection of feline leukemia virus p27 antigen. 2854 72

Moloney leukemia virus 10 (MOV10) is an RNA helicase that has been shown to affect the replication of several viruses. The effect of MOV10 on Hepatitis B virus (HBV) infection is not known and its role on the replication of this virus is poorly understood. We investigated the effect of MOV10 down-regulation and MOV10 over-expression on HBV in a variety of cell lines, as well as in an infection system using a replication competent virus. We report that MOV10 down-regulation, using siRNA, shRNA, and CRISPR/Cas9 gene editing technology, resulted in increased levels of HBV DNA, HBV pre-genomic RNA, and HBV core protein. In contrast, MOV10 over-expression reduced HBV DNA, HBV pre-genomic RNA, and HBV core protein. These effects were consistent in all tested cell lines, providing strong evidence for the involvement of MOV10 in the HBV life cycle. We demonstrated that MOV10 does not interact with HBV-core. However, MOV10 binds HBV pgRNA and this interaction does not affect HBV pgRNA decay rate. We conclude that the restriction of HBV by MOV10 is mediated through effects at the level of viral RNA.
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PMID:Effects of Moloney Leukemia Virus 10 Protein on Hepatitis B Virus Infection and Viral Replication. 3131 55

The NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ strain (NOD scid gamma, NSG) is a severely immunodeficient inbred laboratory mouse used for preclinical studies because it is amenable to engraftment with human cells. Combining scid and Il2rgnull mutations results in severe immunodeficiency by impairing the maturation, survival, and functionality of interleukin 2-dependent immune cells, including T, B, and natural killer lymphocytes. While NSG mice are reportedly resistant to developing spontaneous lymphomas/leukemias, there are reports of hematopoietic cancers developing. In this study, we characterized the immunophenotype of spontaneous lymphoma/leukemia in 12 NSG mice (20 to 38 weeks old). The mice had a combination of grossly enlarged thymus, spleen, or lymph nodes and variable histologic involvement of the bone marrow and other tissues. All 12 lymphomas were diffusely CD3, TDT, and CD4 positive, and 11 of 12 were also positive for CD8, which together was consistent with precursor T-cell lymphoblastic lymphoma/leukemia (pre-T-LBL). A subset of NSG tissues from all mice and neoplastic lymphocytes from 8 of 12 cases had strong immunoreactivity for retroviral p30 core protein, suggesting an association with a viral infection. These data highlight that NSG mice may develop T-cell lymphoma at low frequency, necessitating the recognition of this spontaneously arising disease when interpreting studies.
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PMID:Morphologic and Immunohistochemical Characterization of Spontaneous Lymphoma/Leukemia in NSG Mice. 3173 41


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