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)

Adult C57BL/10 mice (H-2b Fv-1b) inoculated with LP-BM5 murine leukemia virus develop a disease which has many features in common with human acquired immunodeficiency syndrome (AIDS), in particular abnormal lymphoproliferation and severe immunodeficiency. In the present study, we examined the possibility that this murine AIDS (MAIDS) model would be useful for evaluating antiretrovirus drugs in vivo through the use of a well-defined antiretrovirus drug, the reverse transcriptase (RT) inhibitor (H. Mitsuya, K.J. Weinhold, P.A. Furman, M.H. St. Claire, S. Nusinoff-Lehrman, R.C. Gallo, D. Bolognesi, D.W. Barry, and S. Broder, Proc. Natl. Acad. Sci. USA 82:7096-7100, 1985) 3'-azido-3'-deoxythymidine (AZT). We evaluated the effect of AZT treatment on de novo virus infection as well as on the induction of immunodeficiency by various parameters, including RT activity in serum, splenomegaly, proliferative responses against alloantigens and mitogens, soluble-antigen-presenting cell activity, and immunoglobulin G levels in serum. Our results demonstrated that AZT treatment of C57BL/10 mice infected with LP-BM5 murine leukemia virus efficiently prevented the induction of immunodeficiency if started at the time of virus inoculation. Starting AZT treatment 1 week later provided only a partial protective effect. Starting AZT treatment 2 weeks later was associated with suppression of RT activity in serum but no prevention of immunosuppression. This MAIDS model may allow rapid and cost-effective screening for antiretrovirus drugs targeted against retroviral functions shared between human AIDS and MAIDS, such as those encoded by gag, pol, or env.
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PMID:3'-Azido-3'-deoxythymidine prevents induction of murine acquired immunodeficiency syndrome in C57BL/10 mice infected with LP-BM5 murine leukemia viruses, a possible animal model for antiretroviral drug screening. 169 56

The Hardy-Zuckerman 4 feline sarcoma virus (HZ4-FeSV), isolated from a feline fibrosarcoma, is a replication defective acute transforming feline retrovirus that originated by transduction of feline c-kit sequences with feline leukemia virus (FeLV). The v-kit sequences of the HZ4-FeSV, a segment of 1106 nucleotides, correspond to sequences of the cytoplasmic domain of the c-kit receptor kinase. The HZ4-FeSV is known to encode an 80-kilodalton protein with FeLV gag and kit determinants. The P80gag-kit protein and its associated activities from HZ4-FeSV-transformed mink cells were characterized. The P80gag-kit protein was found to be myristoylated, suggesting a membrane association for this protein. In agreement with the predicted relationship with tyrosine kinases, by using the in vitro immune complex-kinase procedure, the P80gag-kit protein was shown to display a tyrosine-specific autophosphorylation activity. In vivo, the P80 protein was found to be phosphorylated on serine and threonine and to a lesser degree on tyrosine. In addition, potential in vivo protein substrates for tyrosine-specific phosphorylation mediated by the P80gag-kit kinase were identified in HZ4-FeSV-transformed cells.
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PMID:Tyrosine protein kinase activity of the HZ4-feline sarcoma virus P80gag-kit-transforming protein. 169 69

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

Glutamine depletion strongly inhibits the replication of Rauscher murine leukaemia retrovirus (RLV) in vitro. Pseudomonas 7A glutaminase-asparaginase (PGA), capable of depleting glutamine and asparagine for prolonged periods, was used to determine the therapeutic effectiveness of glutamine depletion in mice infected with RLV or Friend virus. During PGA treatment of viraemic animals, serum reverse transcriptase activity fell to control levels and infected animals did not develop splenomegaly. The therapeutic results obtained with PGA compared favourably with those of azidothymidine given intraperitoneally at 30 mg/kg/day. Western blots performed on splenic tissue from control and treated animals indicated that glutamine depletion prevented readthrough of an amber codon at the gag-pol junction, stopping translation of viral mRNA at that point. Treatment of RLV-infected animals with PGA resulted in nearly a 200% increase in mean survival time even when therapy was initiated late in the course of the disease. To our knowledge, this is the first demonstration that a nutrient required for viral replication can be enzymically depleted in vivo to inhibit viral replication.
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PMID:Inhibition of mouse retroviral disease by bioactive glutaminase-asparaginase. 170 10

We have previously shown that strong epitopes recognized by anti-Friend virus (FV) cytotoxic T lymphocytes (CTL) in H-2b mice are encoded in both the env and gag/pol regions of the helper friend leukemia virus genome. Two approaches have been used to identify these epitopes. At the nucleic acid level, we have constructed env genes with either of two in-frame deletions: pKR2, an env gene with a 681-bp deletion in the gp70 region and inserted into the pSV2-gpt-1 expression vector; and pKR1, an env gene with an 81-bp deletion in the p15E region and inserted into pSV2-gpt-1. Cell clones were established by transfecting Fisher rat embryo cells with pDb (the H-2Db restriction element), pNEO (for G418 selection) and either pKR1 or pKR2. Db and env gene expression was monitored by immunoprecipitation with polyclonal antibodies or by detection of viral RNA on Northern blots. Expressor cell clones were tested for susceptibility to lysis by polyclonal anti-FV/Db CTL in 51Cr-release assays. Whereas cells expressing pKR1 were lysed to the same extent as cells expressing the intact env gene, cells expressing pKR2 were resistant to lysis, suggesting that all detectable env epitopes are encoded within the 681-bp deletion. Polypeptides representing the two most likely candidate epitopes encoded in this segment were synthesized and tested for their abilities to sensitize FRE cells expressing Db alone for lysis by the CTL. One 17-mer polypeptide, AGTGDRLLNLVQGAYQA [corrected], functioned as a strong CTL epitope in this assay, but the other 18-mer polypeptide was inactive. Studies of the role of this epitope in the immune response to candidate viral vaccines are in progress.
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PMID:Identification of an epitope encoded in the env gene of Friend murine leukemia virus recognized by anti-Friend virus cytotoxic T lymphocytes. 170 62

To generate nonpathogenic viral particles which express active human immunodeficiency virus type 1 (HIV-1) protease (PR), plasmids containing sequences from the genomes of HIV-1 and Moloney murine leukemia virus (M-MuLV) were constructed. Either the PR coding region alone; the gag, PR, and reverse transcriptase protein-coding regions; or the complete gag and pol protein-coding regions from HIV-1 were substituted for the corresponding regions of a full-length M-MuLV clone to yield the chimeric plasmids pMoHIV-I, pMoHIV-III, and pMoHIV-IV, respectively. Cell lines which express the viral gag polyprotein were isolated for hybrids pMoHIV-I and pMoHIV-III. These cells produced viral particles which contained processed core proteins. Cleavage of the gag polyprotein in the viral particles was inhibited by the HIV-1 PR inhibitor L-687908, indicating that the viral PR is responsible for the observed processing. The hybrid virions were not infectious; analyses indicated that the viral particles contained little or no reverse transcriptase activity. In addition, particles produced by pMoHIV-III transfectants failed to package the viral genomic RNA. The cell line which expresses and processes the HIV-1 gag polyprotein is a safe and effective reagent for the in vivo evaluation of potential inhibitors of the HIV-1 PR.
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PMID:Expression of active human immunodeficiency virus type 1 protease by noninfectious chimeric virus particles. 170 93

Using sera from hosts infected with bovine leukaemia virus (BLV), human T cell lymphoma virus types I and II (HTLV-I and -II), or simian T cell lymphoma virus type I (STLV-I), we found that the major gag proteins of these viruses cross-react immunologically. The specificity of this cross-reactivity was demonstrated by absorption using purified viral proteins, virus lysates and extracts of infected cells. The data strongly suggested that the cross-reacting epitope(s), referred to as CE, differs from those responsible for cross-reactions between the major gag proteins of HTLV-I, HTLV-II and STLV-I, and between those of BLV and HTLV-I reported previously. The prevalence of antibodies to CE was low, even amongst infected hosts with high titres to other epitopes present in the major gag proteins of the homologous viruses. CE was not detected in any of the other C- or D-type retroviruses, or lentiviruses examined. Therefore, it is likely that CE can be used to define serologically a subgroup of C-type retroviruses, the genomes of which display unique features and functional activities.
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PMID:The trans-activating C-type retroviruses share a distinct epitope(s) that induces antibodies in certain infected hosts. 171 53

To study the possible involvement of a murine leukemia virus (MuLV) related agent in human cancer, an extensive immunoblotting analysis of human sera (cancer, autoimmune as well as control normal ones) for the presence of antibodies to MuLV structural proteins was performed. Out of 350 sera, 89 reacted with gag precursor Pr65, 72 reacted with major viral core protein p30 and five with the matrix protein p15. Antibody reactivity to the env-encoded glycoprotein gp70 was detected in 7 cases out of 16 sera tested. There were no significant differences between pathological and normal sera concerning the patterns and the frequency of the reactivity. Sera from patients with various malignancies (mainly with breast cancer) generally displayed more intensive signals to MuLV p30 than normal sera. Epitope mapping revealed that MuLV p30-reactive antibodies recognize an antigenic determinant(s) located at the carboxyterminus of the protein.
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PMID:High prevalence of circulating antibodies to MuLV p30 antigen in human sera. An autoimmune response? 172 Feb 1

v-erb-B is the principal transforming gene of avian erythroblastosis virus, a replication defective retrovirus that transforms erythroid and fibroblast cells in vitro and causes erythroleukemia and fibrosarcoma in vivo. We have used a recombinant murine retrovirus, based on the truncated genome of Moloney murine leukemia virus and containing a chimeric gag-v-erb-B gene, to determine the murine hematopoietic cells transformed by v-erb-B. Infection of day 16.5 murine embryonal cells in liquid culture with this virus resulted in the outgrowth of foci of loosely to non-adherent hematopoietic cells which grew in close association with an adherent monolayer. After several weeks in culture a clonal population of transformed pre-B-lymphocytes emerged from this transformation initiated, though still growth factor dependent, population. These transformed cells were growth factor independent, and were tumorigenic in syngeneic mice. The results indicate that although v-erb-B can initiate transformation of murine hematopoietic cells, additional events are required for establishment of the fully transformed growth factor independent, tumorigenic phenotype. This v-erb-B induced progression from growth factor dependence to independence provides an in vitro model system for analysing events involved in the initiation and maintenance of leukemia.
Leukemia 1992 Jan
PMID:Transformation of murine pre-B-lymphocytes by v-erb-B: progression to growth factor independence and tumorigenicity. 173 10

Human T-cell leukemia virus type I (HTLV-I) genome is believed to encode its own protease, although the protease has not yet been detected. To identify the HTLV-I protease, an in-frame gag (3' portion)-prt region was expressed in Escherichia coli. The 14-kDa product was detected using antisera against a synthetic peptide mimicking the fragment of HTLV-I protease, although the molecular weight of the primary translational product was 27,000. A cell extract had a proteolytic activity to cleave a synthetic peptide substrate containing the cleavage site of gag p19/p24 at the correct site in vitro. Replacement of the putative active site Asp-64 with Gly abolished both in vivo processing activity and in vitro proteolytic activity. These results suggest that the 14-kDa product is the mature enzymatically active HTLV-I protease generated through posttranslational autoprocessing in E. coli.
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PMID:Expression of human T-cell leukemia virus type I protease in Escherichia coli. 176 78


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