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)

The life cycle of enveloped viruses is intimately associated with, and influenced by, host cell membrane organization, which is altered by hyperthermia. Hyperthermia-modified Moloney murine leukaemia virus (M-MuLV) release, protein production and intracellular protein processing in a chronically infected cultured murine cell line, C9CL98 (C9). Both 44 degrees C/45 min and 42.8 degrees C/135 min substantially decreased cell-free viral env protein 8-48 h postheating, but virus release and cellular viral protein content increased following 42.8 degrees C/25 min. Proteolytic processing of viral Pr65 gag precursor to p30 gag protein, normally observed within unheated C9 cells, was blocked for at least 8 h after 44 degrees C/45 min. Virus released from heated C9 cells was as infectious to NIH/3T3 cells as was virus from control cells. Cells surviving exposure to 42.8 degrees C/135 min became thermotolerant to decreased virus release from a second heating if delivered 10-48 h after the initial heating. The mechanism by which virus release is blocked after hyperthermia remains to be elucidated.
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PMID:Effect of heat on viral protein production and budding in cultured mammalian cells. 780 20

The aetiology of LGL leukaemia is now known; however, we recently detected HTLV-II from such a patient. We describe here the occurrence of LGL leukaemia in a mother and her son. Serum from the son reacted to HTLV-I/II gag proteins, but not a recombinant HTLV-I env protein p21e; serum from the mother was negative. PCR analyses in both patients were negative for pX and pol sequences shared by HTLV-I/II and also for specific gag sequences of HTLV-I and HTLV-II. These data show that familial cases of LGL leukaemia are not associated with prototypical HTLV-I or HTLV-II infection.
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PMID:Familial occurrence of LGL leukaemia. 794 47

The development of retroviral vectors that target specific cell types could have important implications for the design of gene therapy strategies. A chimeric protein containing the polypeptide hormone erythropoietin and part of the env protein of ecotropic Moloney murine leukemia virus was engineered into the virus. This murine virus became several times more infectious for murine cells bearing the erythropoietin receptor, and it also became infectious for human cells bearing the erythropoietin receptor. This type of tissue-specific targeting by means of ligand-receptor interactions may have broad applications to a variety of gene delivery systems.
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PMID:Tissue-specific targeting of retroviral vectors through ligand-receptor interactions. 797 23

Endogenous feline leukemia virus (FeLV)-related sequences (enFeLV) are a family of proviral elements found in domestic cats and their close relatives. These elements can recombine with exogenous, infectious FeLVs of subgroup A (FeLV-A), giving rise to host range variants of FeLV-B. We found that a subset of defective enFeLV proviruses is highly expressed in lymphoma cell lines and in a variety of primary tissues, including lymphoid tissues from healthy specific-pathogen-free cats. At least two RNA species were detected, a 4.5-kb RNA containing gag, env, and long terminal repeat sequences and a 2-kb RNA containing env and long terminal repeat sequences. Cloning of enFeLV cDNA from two FeLV-free lymphoma cell lines (3201 and MCC) revealed a long open reading frame (ORF) encoding a truncated env gene product corresponding to the N-terminal portion of gp70env. Interestingly, all of three natural FeLV-B isolates include 3' env sequences which are missing from the highly transcribed subset and hence must be derived from other enFeLV elements. The enFeLV env ORF cDNA clones were closely similar to a previously characterized enFeLV provirus, CFE-16, but were polymorphic at a site corresponding to an exogenous FeLV neutralization epitope. Site-specific antiserum raised to a C-terminal 30-amino-acid peptide of the enFeLV env ORF detected an intracellular product of 35 kDa which was also shed from cells in stable form. Expression of the 35-kDa protein correlated with enFeLV RNA levels and was negatively correlated with susceptibility to infection with FeLV-B. Cell culture supernatant containing the 35-kDa protein specifically blocked infection of permissive fibroblast cells with FeLV-B isolates. We suggest that the truncated env protein mediates resistance by receptor blockade and that this form of enFeLV expression mediates the natural resistance of cats to infection with FeLV-B in the absence of FeLV-A.
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PMID:Defective endogenous proviruses are expressed in feline lymphoid cells: evidence for a role in natural resistance to subgroup B feline leukemia viruses. 813 99

As an approach to cell targeting by retroviruses, the lack of which constitutes one major limitation of retroviral vector technology, we engineered the Moloney murine leukemia virus ecotropic envelope glycoprotein. When inserted between amino acids 6 and 7 of the latter, a single-chain antibody fragment (ScFv) specific for human major histocompatibility complex class I molecules was shown to be able to redefine the tropism of ecotropic Moloney murine leukemia virus-derived retroviral particles by allowing infection of major histocompatibility complex class I-positive human cells. At variance with other recently described experimental systems, the type of modification adopted here allowed targeted infection in the absence of coexpressed wild-type env-encoded protein molecules. Interestingly, the chimeric ScFv-env protein also retained the ability to recognize the ecotropic receptor and allowed infection of murine cells, albeit at a reduced efficiency.
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PMID:Targeted infection of human cells via major histocompatibility complex class I molecules by Moloney murine leukemia virus-derived viruses displaying single-chain antibody fragment-envelope fusion proteins. 862 71

Natural killer (NK) cells are CD3- large granular lymphocytes (LGL) responsible for immunity against viral infections. A chronic lymphoproliferative disorder of NK cells has been described in which the expanded NK cells display a restricted phenotype and cytotoxic activity. These data raise the hypothesis that proliferating LGL in these patients result from discrete expansions of NK cells responding to an unknown, perhaps viral, antigen. Recently, it was found that mice transgenic for the tax gene of human T-cell leukemia/lymphoma virus (HTLV) develop NK leukemia. Therefore, we studied 15 patients with chronic NK lymphoproliferative disorder for evidence of HTLV infection. Sera were tested using an HTLV-I/II-enzyme linked immunosorbent assay and a modified Western blot assay containing recombinant env proteins. None of the sera met conventional criteria for HTLV seroreactivity. However, sera from 11 patients (73%) reacted with the recombinant HTLV env protein p21E. The anti-p21E reactivity of these sera was then mapped employing the recombinant proteins GD21 and BA21. No reactivity to the immunodominant HTLV epitope GD21 was observed, suggesting that prototypical HTLV infection is unlikely in these patients. This was confirmed by finding no evidence for HTLV nucleic acids by PCR analyses employing primers specific for conserved regions in the env, pol, and pX genes. In contrast, 10 of the 15 sera reacted with the epitope BA21, documenting for the first time an association between a unique seroreactivity and disease. The high incidence of BA21 seroreactivity in these patients suggests that exposure to a protein containing homology to BA21 may be important in the pathogenesis of this lymphoproliferative disorder.
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PMID:Seroreactivity to an envelope protein of human T-cell leukemia/lymphoma virus in patients with CD3- (natural killer) lymphoproliferative disease of granular lymphocytes. 929 32

Targeted gene delivery to vascular lesions is a major challenge in the development of gene therapy protocols for cardiovascular diseases. One approach would be to enable retroviral vectors to accumulate at sites of vascular injury and enhance local vector concentration. An early step in wound repair is the adhesion of platelets to collagen exposed from damaged vasculature. Hence, the Moloney murine leukemia virus (MoMLV) envelope (env) protein was engineered to incorporate a high-affinity collagen-binding domain derived from von Willebrand clotting factor, and expressed in Escherichia coli and in mammalian cells. The chimeric env protein bound tightly to collagen, and virions bearing this collagen-binding env protein exhibited viral titers approaching those of virions expressing wild-type (WT) env protein. The chimeric virions were concentrated on collagen matrices, and they retained their infectivity under conditions in which virions bearing WT env protein were washed away. Targeted delivery of the chimeric env protein to injured mouse aorta and selective binding of the collagen-targeted virions to injured rabbit artery were observed. In comparative studies, vascular smooth muscle cell transduction was demonstrated in catheter-injured carotid arteries following infusion of collagen-targeted virions but not of virions bearing WT env protein. Taken together, these observations demonstrate the ability of collagen-targeted virions to localize gene delivery to sites of vascular injury.
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PMID:Targeting retroviral vectors to vascular lesions by genetic engineering of the MoMLV gp70 envelope protein. 944 72

Retrovirus genomes express, among other products, the envelop (env) proteins SU (gp70) and TM (p15E). They coexist at the viral surface membrane and are able to promote immunosuppression and membrane fusion. In mouse oocytes, endogeneous retroviruses (ERV) genomes are expressed at fertilization, and antigen epitopes of the Moloney murine leukemia virus (MuLV) env protein gp70 are recognized in the cytoplasm of the oocytes before but not after fertilization. By using a panel of monoclonal antibodies (mAbs) raised against env components, we checked with laser scanning confocal microscopy (LSCM) whether gp70 and p15E were expressed also on the oocyte surface membrane (oolemma). Since we found that both mouse and human unfertilized oocytes expressed these ERV proteins on the oolemma and that the expression enfeebled significantly after fertilization, we assume that ERV genomes could play a role at the sperm-egg binding and fusion.
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PMID:Expression of envelope proteins of endogeneous C-type retrovirus on the surface of mouse and human oocytes at fertilization. 1040 97

Human T-cell leukaemia virus type I (HTLV-I)-transformed rabbit T-cells, F647a, were intraperitoneally injected into eight 10-week-old C3H/He and C3H/HeJ mice (1 x 10(7) F647a cells/mouse), respectively. Antibody titres against HTLV-I increased to a peak at 1-3 months after injection in both C3H/He and C3H/HeJ mice. At 12 months after injection, antibody titres of two of the eight C3H/HeJ mice became undetectable, whereas those of all the C3H/He mice still ranged from 1:10 to 1:40. Sera from both seropositive C3H/He and C3H/HeJ mice reacted with HTLV-I core proteins, but not with the env protein. HTLV-I proviral sequences were detected in two of eight C3H/He mice and three of the eight C3H/HeJ mice. These results suggest that HTLV-I is able to infect an adult mouse.
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PMID:Transmission of human T-cell leukaemia virus type I into adult mice. 1107 67

Targeting retroviral vectors to tumor vasculature is an important goal of cancer gene therapy. In this study, we report a novel targeting approach wherein IgG-binding peptides were inserted into the Moloney murine leukemia virus (MuLV) envelope (env) protein. The modifications on the viral env included replacement of the entire receptor binding region of the viral env with protein A (or ZZ) domains. The truncated env incorporating IgG-binding motifs (known as proteins) provided the targeting function, while the co-expressed wild-type (WT) env protein enabled viral fusion and cell entry. An anti-human VEGF receptor (Flk-1/KDR) antibody served as a molecular bridge, directing the retroviral vector to the endothelial cell. Hence, the IgG-targeted vectors bound to the Flk-1/KDR antibody which in turn bound to VEGF receptors on Kaposi sarcoma, KSY1, endothelial cells. The net effect was increased viral fusion and infectivity of IgG-bound retroviral vectors when compared to non-targeted vectors bearing WT env alone. These data provide the proof of concept that IgG-binding vector/VEGF receptor antibody complexes may be used to enhance retroviral gene delivery to activated endothelial cells.
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PMID:Retroviral vectors bearing IgG-binding motifs for antibody-mediated targeting of vascular endothelial growth factor receptors. 1156 69


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