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)

Derived from the susceptible AKR.H-2bSL1 tumor cell line, a variant tumor subclone, cl.18-5, was selectively insusceptible to H-2-restricted anti-AKR/Gross virus cytotoxic T lymphocytes (CTL) due to its failure to be recognized. In this study, the expression of virus-related products by variant cl.18-5 cells was compared to that of AKR.H-2bSL1 cells and a susceptible clone, as an approach towards defining the virus-associated antigens recognized by anti-AKR/Gross virus CTL. Despite the type specificity of the CTL, cl.18-5 displayed normal levels of the group-specific antigen (gag) encoded proteins p30, p15, p12 and p10, and the gag-associated Gross cell surface antigen. These results were confirmed by fluorescence-activated cell sorter analysis employing monoclonal antibodies specific for either AKR p12 or the cell surface glycosylated form of AKR ecotropic gag product. In contrast, cl.18-5 was variably less sensitive than AKR.H-2bSL1 to the action of complement and xenogeneic antisera directed against the envelope (env) product gp70. In addition, a panel of five monoclonal antibodies to gp70, which detect distinct endogenous ecotropic viral determinants, lysed AKR.H-2bSL1, but not cl.18-5 cells. However, absorption experiments indicated that cl.18-5 did express near normal levels of these specificities, suggesting an alteration in the orientation or topographical distribution of these determinants. Consistent with an inappropriate display of env products, cl.18-5 was found to be deficient in the production of infectious ecotropic leukemia virus. The particulate fraction of the cell-free supernatant of cl.18-5 contained normal levels of reverse transcriptase activity, indicating that noninfectious viral particles were being produced. Collectively, these results point to an association between recognition by anti-AKR/Gross virus CTL and the expression of ecotropic gp70 required for infectivity of virus.
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PMID:The specificity of H-2-restricted cytotoxic T lymphocytes directed to AKR/Gross leukemia virus-induced tumors. II. Altered gp70 display and production of noninfectious virus particles by an insusceptible variant tumor. 619 7

We have constructed a series of deletion mutations in the p30 and p10 domains of the gag gene of Moloney murine leukemia virus. Mutants with deletions in P30 were completely defective in virion particle production even though an altered gag precursor protein is synthesized. This domain is apparently critical for particle formation. A mutant in P10 was able to release virion particles into the medium, and low levels of reverse transcriptase activity could be detected in these virions. To explore the effects of these mutations on the utilization of the gag-pol precursor, we have introduced these mutants into cells already releasing defective particles from an endogenous provirus which directs the synthesis of gag gene products and not pol gene products. The P10 mutant was capable of providing pol function as judged by the incorporation of high levels of reverse transcriptase into the particles and complete complementation for XC plaque formation. In contrast, the mutants in P30 were negative in this complementation test. Thus, those gag mutants which were unable on their own to assemble virion particles were also unable to contribute the gag-pol precursor to these particles. These mutations are the first to be mapped to the gag region which affect pol function, suggesting that the gag-pol precursor must be assembled before pol is functionally separated from the gag domain. The concordance of the effects of different mutations on both particle formation and gag-pol utilization suggests that similar domains of gag (namely, domains in the P30 region) are needed for these two processes.
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PMID:Mutations in the gag gene of Moloney murine leukemia virus: effects on production of virions and reverse transcriptase. 619 13

Mink cells nonproductively-infected with the weakly-transforming T-8 isolate of murine leukemia virus (MuLV) express a 110,000 mol wt polyprotein designated T-8 P110. By immunoprecipitation analysis, T-8 P110 is shown to contain AKR-MuLV amino terminal gag gene-specific components (p15, p12) but to lack p30, p10, gp70, and p15(E) antigenic determinants. These observations are further substantiated by tryptic peptide analysis indicating T-8 P110 to share approximately six lysine-containing tryptic peptides with AKR-MuLV Pr65gag, and none with AKr-MuLV Pr82env. Furthermore, of seven methionine-containing T-8 P110 tryptic peptides, at least four can be conclusively shown not to be present in either AKr-MuLV Pr180gag/pol or Pr82env. A clonal mink cell line nonproductively infected by T-8, and expressing high levels of P110, although not morphologically transformed, is shown to lack elevated levels of tyrosine-specific protein kinase activity and reduction of epidermal growth factor binding sites characteristic of cells transformed by many other RNA-transforming viruses. These findings argue either that the T-8 viral genome contains acquired cellular sequences encoding a portion of P110, or that T-8 P110 represents an inphase deletion of AKR-MuLV Pr180gag/pol with extensive posttranlational modification and that an as yet unidentified protein is responsible for T-8 associated transformation.
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PMID:Identification of tryptic peptides unique to a 110,000-molecular weight polyprotein encoded by the T-8 isolate of murine leukemia virus. 625 65

Preparations of purified Rauscher murine leukemia virus were found to contain an endodeoxyribonuclease after disruption of the virus with nonionic detergents. The enzyme makes single-strand breaks in linear or covalently closed circular phage double-stranded DNA molecules. The enzyme was partially purified by ion-exchange chromatography on DEAE- and carboxymethyl-Sepharose columns followed by electrophoresis in DNA-containing polyacrylamide gels. The enzyme was separated from reverse transcriptase (p80pol), and the final endonuclease preparation contained no detectable reverse transcriptase activity. The DEAE-Sepharose column-purified endonuclease activity contained a polypeptide of about 40,000 Mr that we term p40. Peptide mapping experiments demonstrated that p40 shares methionine-labeled tryptic peptides with Pr200gag-pol and Pr135pol. Six major methionine-labeled tryptic peptides derived from p40 were found in Pr200gag-pol, but only five of these were detected in Pr135pol. The four core proteins (p30, p15, pp12, and p10) and p80pol plus p40 account for most, but not all, of the peptide sequences of Pr200gag-pol. The endonuclease-associated p40 is similar in size and precursor origin to the avian retrovirus-coded endonuclease (p32). In view of these similarities to the avian p32 endonuclease and its association with partially purified Rauscher murine leukemia virus-associated endonuclease preparations, we propose that p40 is the Rauscher murine leukemia virus-coded endonuclease.
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PMID:Endodeoxyribonuclease activity associated with Rauscher murine leukemia virus. 626 Sep 82

Murine leukemia viruses contain a low molecular weight basic protein, designated p10, which binds to single-stranded nucleic acids. The complete amino acid sequence of p10 from the Rauscher strain of virus has been determined. The partial amino acid sequences of p10s from Moloney, Friend, AKR, Gross, radiation leukemia, and BALB/2 viral strains have also been determined using microsequencing techniques. Rauscher p10 is composed of 56 amino acid residues; the other p10s are similar in size but differ from Rauscher by a few conservative amino acid substitutions. The structure of Rauscher p10 was compared to the structure of a functionally homologous protein from Rous avian sarcoma virus. The comparison revealed regions of amino acid sequence homologies which indicate a phylogenetic relationship between the murine and avian viral strains. The analyses revealed a periodic placement of three Cys residues and a Gly-His sequence. A structure involving these residues is found once in the murine protein and twice in the avian protein. A similar structure is seen in the single stranded nucleic acid binding protein of bacteriophage T4. However, in the latter case, the order of amino acid residues is inverted.
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PMID:Primary structure of the low molecular weight nucleic acid-binding proteins of murine leukemia viruses. 626 42

A cell line (LB59Ly) derived from the leukocytes of a leukaemic cow was established as a monolayer, which spontaneously released large amounts of a retrovirus. This virus was found to be indistinguishable from the bovine leukaemia virus (BLV) produced by the commonly used high-producing heterologous cell line (FLK-BLV). Like the latter, its reverse transcriptase activity was greater in the presence of Mg2+ cations than in the presence of Mn2+ cations; its polyacrylamide gel electrophoresis pattern showed the presence of gp51, p24, p15, p12 and p10, and the antigenicity of the two major proteins completely cross-reacted with those of BLV from FLK-BLV cells. The virus was infectious and induced early and late polykaryocytosis, the specificity of which was demonstrated by use of specific anti-BLV sera.
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PMID:Establishment and propagation of a bovine leukaemia virus-producing cell line derived from the leukocyte of a leukaemic cow. 627 Feb 54

The intracellular precursor polyproteins of simian sarcoma-simian-associated virus [SiSV(SiAV)] were compared to the intracellular proteins of the human retrovirus isolates. HL23V, HEL12V and A1476V, by radioimmunoprecipitation followed by SDS-polyacrylamide gel electrophoresis and tryptic peptide analysis. Cells infected with SiSV(SiAV) were characterized by polyproteins Pr200gag-pol, gPr80env, Pr80gag, Pr60gag and Pr40gag. Identical intracellular precursor polyprotein profiles were obtained from cells infected with HL23V, HEL12V and A1476V. Tryptic digest mapping of peptides containing [3H]leucine showed the structural composition of Pr60gag to be the virus core proteins, p28, p15/p12 and p10. The SiSV(SiAV) envelope precursor, gPr80env, contained the structural determinants of mature viral gp70 and a non-glycosylated protein termed p15E. The homology of the human isolate viruses, HL23V, HEL12V and A1476V, to the SiSV(SiAV)/GaLV (gibbon ape leukaemia virus) family of viruses was confirmed by mapping studies. Both gPr80env and Pr60gag of SiAV were identical by tryptic peptide mapping to the respective proteins from the three human retrovirus isolates examined. The potential significance of these results to considerations of the origins of SiAV and the SiAV-like human isolates is discussed.
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PMID:A comparison of the intracellular precursor polyproteins of simian sarcoma-associated virus [SiSV(SiAV)] and three human virus isolates: HL23V, HEL12V and A1476V. 629 May 96

We have recently found that, in vitro, the murine leukaemia virus (MuLV)-associated protein kinase activity predominantly phosphorylates Pr65gag, a virus protein present in relatively small amounts in partially purified virus preparations. Other virus proteins, such as p10, Pr27gag and Pr40gag, are also phosphorylated in vitro, but to a lesser degree. Furthermore, when immature core subparticles which are enriched in Pr65gag are prepared from virions by Sepharose 6B exclusion column chromatography, about 50% of the kinase activity (as assayed with the exogenous substrate phosvitin) remains associated with the cores. We report here that this core-associated activity is distinct from Pr65gag since it can be separated from Pr65gag by chromatography on denatured DNA--cellulose columns followed by centrifugation of the 0.2 M-NaCl-eluted fraction. Under these conditions, Pr65gag is pelleted while the kinase activity, which can phosphorylate both endogenous (MuLV Pr65gag and p10) as well as exogenous (phosvitin) substrates, remains in the supernatant. Interestingly, when the amount of Pr65gag is reduced, as in such preparations, p10 then becomes more heavily phosphorylated.
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PMID:Separation of a murine leukaemia virus protein kinase activity from its Pr65gag polyprotein substrate after DNA--cellulose chromatography. 629 9

The nucleic acid-binding proteins of bovine leukemia virus (BLV) and feline leukemia virus (FeLV) were isolated in a high state of purity with chloroform-methanol extraction followed by reversed-phase liquid chromatography. Selective solubilization and purity of BLV p12 and FeLV p10 was confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The compositions and molecular weights were determined by amino acid analysis. An abundance of lysine and arginine residues along with their size identifies both BLV p12 and FeLV p10 as small basic proteins similar to well-defined type C viral nucleoproteins. NH2-terminal degradation by the semiautomated Edman method provided the sequence of the first 40 amino acids for both proteins. The putative nucleic acid binding site found in several type C viral nucleoproteins was contained within this sequence, with the most homology centered around an eight-amino acid region involving seven identical residues and one substitution. Antisera were developed in rabbits, and specificity and titers were determined by electroblotting and immunoautoradiography. By this technique, an immunological cross-reaction was found between BLV p12 and FeLV p10. The shared antigenic determinant most likely exists in the highly conserved eight-amino acid region. Although this sequence is also highly conserved in the nucleic acid-binding proteins of murine leukemia viruses, the shared antigenic determinant is not found in these or any other type C viruses tested. It is suggested that substitution of arginine (BLV p12/FeLV p10) to lysine (murine leukemia virus p10) is sufficient to elicit a change in antibody specificity.
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PMID:Structural and antigenic analysis of the nucleic acid-binding proteins of bovine and feline leukemia viruses. 629 55

Twenty-six different murine leukemia virus (MuLV)-related clones have been isolated from a human DNA library and characterized by restriction enzyme mapping and reciprocal nucleic acid hybridization reactions. The sequence of approximately 2,600 nucleotides, spanning more than 4.0 kilobases, of one of the MuLV-related cloned human DNAs was also determined. The deduced amino acid sequence permitted the alignment of this prototype cloned human DNA segment with the p12 gag, p30 gag, p10 gag, and pol regions of Moloney MuLV. A majority of the endogenous type C retrovirus-related segments present in human DNA are approximately 6.0 kilobases in size and appear to contain a deletion of env sequences.
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PMID:Characterization and partial nucleotide sequence of endogenous type C retrovirus segments in human chromosomal DNA. 629 69


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