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)

We have identified p10 as a fifth gag protein of avian sarcoma and leukemia viruses. Amino-terminal protein sequencing of this polypeptide purified from the Prague C strain of Rous sarcoma virus and from avian myeloblastosis virus implies that it is encoded within a stretch of 64 amino acid residues between p19 and p27 on the gag precursor polypeptide. For p10 from the Prague C strain of Rous sarcoma virus the first 30 residues were found to be identical with the predicted amino acid sequence from the Prague C strain of Rous sarcoma virus DNA sequence, whereas for p10 from avian myeloblastosis virus the protein sequence for the same region showed two amino acid substitutions. Amino acid composition data indicate that there are no gross composition changes beyond the region sequenced. The amino terminus of p10 is located two amino acid residues past the carboxy terminus of p19, whereas its carboxy terminus probably is located immediately adjacent to the first amino acid residue of p27.
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PMID:Amino-terminal amino acid sequence of p10, the fifth major gag polypeptide of avian sarcoma and leukemia viruses. 630 Apr 42

Two revertants of ts110 Moloney murine sarcoma virus (MuSV) with wild-type MuSV phenotype were examined for the presence of mos gene products, ts110 MuSV has a temperature-sensitive defect in a function required to maintain the transformed phenotype. The nonproducer 6m2 cell clone transformed by ts110 produces an 85,000-Da gag-mos protein (P85gag-mos) and a 58,000-Da gag protein (P58gag). A spontaneous revertant (clone 54-5A4) of the 6m2 cell clone produces a 100,000-Da protein (P100) recognized by antisera raised against murine leukemia virus p15, p12, and p30 but lacks determinants of p10, reverse transcriptase, and gp70. P100 was specifically recognized by antisera (anti-C3) prepared against a synthetic peptide representing the predicted C-terminal 12 amino acids of Moloney MuSV v-mos gene. Normal sera or anti-C3 blocked with excess synthetic peptide did not recognize P100. Thus, P100 is a product of the gag and mos genes. P100 was found to be phosphorylated. A second wild-type revertant (clone 204-3) was obtained by superinfection of ts110 nonproducer cells with Simian sarcoma associated virus (SSAV); it was also found to contain a phosphorylated P100gag-mos protein. The 204-3 cell clone also contained two gag polyproteins (Pr60gag and Pr55gag) of the size and antigenic properties of those found in SSAV-infected cells. These results provide two examples of P100 gag-mos proteins both derived from the P85gag-mos producing 6m2 cell clone. The P100 gag-mos polyproteins are made in amounts that are easily detected by radiolabeling experiments using [3H]leucine. The intracellular viral RNAs present in 6m2 cells and the two revertant clones were also examined. All three cell clones contained a 4.0 kb RNA hybridizing to v-mos sequences but only the 6m2 clone contained a 3.5 kb mos-containing RNA. Our findings indicate that the 3.5 kb RNA codes for P85gag-mos in cell-free translation experiments (Junghans et al., 1982, J. Mol. Biol. 161, 229). These findings as they relate to the mechanism that produces P100gag-mos instead of P85gag-mos are discussed.
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PMID:Gag-mos Polyproteins encoded by variants of the Moloney strain of mouse sarcoma virus. 630 90

Murine leukemia virus (MuLV) encodes two independent pathways for expression of the gag gene. One pathway results in processing and cleavage of the precursor Pr65gag to yield the internal capsid proteins of the virion and is analogous to gag polyprotein precursors for all classes of retroviruses. The other pathway, which is not encoded by several other classes of retroviruses, begins with a glycosylated polyprotein gPr80gag . gPr80gag is synthesized independently of Pr65gag; it contains Pr65gag peptides and additional amino-terminal protein. It is modified by further addition of carbohydrate, exported to the cell surface, and released from the cell but does not appear in virus particles. To investigate the role of glycosylated gag in MuLV infection, two mutants of Moloney MuLV (M-MuLV) deficient for synthesis of gPr80gag but able to synthesize Pr65gag were constructed. The mutants were obtained by substitution into a molecular clone of M-MuLV DNA by DNA from two acutely transforming viruses, Ableson MuLV (Ab-MuLV) and Moloney murine sarcoma virus (M-MSV). Both Ab-MuLV and M-MSV are derived from M-MuLV and they express M-MuLV gag sequences, but some strains do not synthesize glycosylated gag protein. For Ab-MuLV, a 177-base-pair Pst I fragment from the P90 strain containing the initiation codon for Pr65gag was substituted for the equivalent fragment in M-MuLV DNA. For M-MSV, 1.5 kilobases at the 5' end of the genome was substituted. Transfection of the recombined DNAs onto NIH-3T3 cells produced infectious M-MuLV, although the infected cells did not produce gPr80gag. Therefore glycosylated gag is not absolutely required for MuLV replication. Deletion of the glycosylated gag pathway did not significantly reduce the level of virus production, although a minor difference in XC plaque morphology was observed.
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PMID:Construction and characterization of Moloney murine leukemia virus mutants unable to synthesize glycosylated gag polyprotein. 631 Jun 8

A series of deletion mutations localized near the 5' end of the Moloney murine leukemia virus genome was generated by site-specific mutagenesis of cloned viral DNA. The mutants recovered from such deleted DNAs failed to synthesize the normal glycosylated gag protein gPr80gag. Two of the mutants made no detectable protein, and a third mutant, containing a 66-base pair deletion, synthesized an altered gag protein which was not glycosylated. All the mutants made normal amounts of the internal Pr65gag protein. The viruses were XC positive and replicated normally in NIH/3T3 cells as well as in lymphoid cell lines. These results indicate that the additional peptides of the glycosylated gag protein are encoded near the 5' end, that the glycosylated and internal gag proteins are synthesized independently, and that the glycosylated gag protein is not required during the normal replication cycle. In addition, the region deleted in these mutants apparently encodes no cis-acting function needed for replication. Thus, all essential sequences, including those for packaging viral RNA, must lie outside this area.
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PMID:Deletion mutants of Moloney murine leukemia virus which lack glycosylated gag protein are replication competent. 660 26

We have shown that the replication of avian sarcoma/leukemia oncornaviruses is not entirely dependent on the metabolic functions of the host cell. It is demonstrated that the proteolytic enzyme which processes the precursor protein pr76 to the group specific antigen (gag) proteins, is virally coded and hence functions independently of cellular activities. It is the gag protein p15 and it cleaves its own precursor. This protease is also able to cleave in vitro the polyprotein of 110 kd which is synthesized in cells non-productively infected with the defective leukemia virus MC29 but not cleaved.
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PMID:Avian oncornaviruses contain a virus coded protease (p15) which processes its own gag protein precursor and the 110 Kd polypeptide of MC29. 745 76

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

Inbred strains of mice differ markedly in their relative susceptibility to the development of lymphoproliferation and immunodeficiency, a syndrome termed mouse AIDS (MAIDS), after infection with the LP-BM5 mixture of murine leukemia viruses (MuLV). The etiologic virus in this mixture is replication defective (BM5def) and encodes only a variant gag protein. Genetic determinants of resistance and susceptibility to induction of MAIDS reside both within and outside the MHC. In strains with C57BL background genes, the MHC haplotypes associated with resistance to disease include d and a, whereas haplotypes b, s, and q are associated with sensitivity. Previous studies showed that MHC class I genes (H-2Dd, H-2Ld) mapping in the D end of H-2 and other genes mapping proximal to the D end determine resistance to MAIDS. This paper examines the nature of these non-D end MHC genes using assays of MHC recombinant and transgenic mice. We demonstrate that expression of E alpha d confers significant resistance to MAIDS, even in mice that do not express H-2Dd/H-2Ld. Unexpectedly, we found that E alpha polymorphisms can significantly influence resistance, with H-2b mice bearing E alpha d as a transgene having greater resistance to MAIDS than mice bearing an E alpha k transgene. E alpha d-mediated resistance to MAIDS was associated with decreased levels of the BM5def genome in splenic DNA, suggesting that E alpha genes exert their effect by enhancing antiviral activity.
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PMID:Influence of H-2 class II antigens on the development of murine AIDS. 814 77

Selection of an optimal promoter is necessary for efficient expression of foreign genes with vaccinia virus. Since a variety of powerful (homologous) vaccinia virus promoters and foreign (heterologous) promoter systems have been described for use in vaccinia, we have addressed the question of whether a general rule exists that allows the prediction of the optimal promoter/gene combination. We have compared the expression properties of four secreted proteins, the human blood clotting factor IX (FIX), the human blood glycoprotein Protein S (ProtS), the human von Willebrand factor (vWF), and the Hepatitis B virus (HBV) middle surface glycoprotein preS2, with proteins that were reported not to be secreted, the HBV large surface glycoprotein preS1 and the murine leukemia virus (MuLV) BM-5 Eco gag protein. In addition, we have included in our study an internal control protein, the vaccinia virus p11 protein, to monitor possible side effects of the promoter system used. Genes encoding the foreign proteins were placed either under control of a synthetic vaccinia virus early/late promoter (selP) or under control of the bacteriophage T7 promoter (T7/emc system). The secreted proteins were more efficiently expressed when fused to the homologous promoter. Direct comparison of the two promoters indicated that the expression level ranged between 1.4 (ProtS) and 3.9 (FIX)-fold higher with the selP than with the T7 promoter. In contrast, the cell-associated HBV preS1 was more efficiently expressed under the T7 promoter and the MuLV BM-5 Eco gag polypeptide was expressed equally well from both promoters. These data indicate that a careful prediction of optimal promoter/foreign gene combinations for the vaccinia virus expression system is possible. The choice of the optimal promoter/expression system is based on a simple classification scheme, discriminating secreted and nonsecreted proteins.
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PMID:Requirements for optimal expression of secreted and nonsecreted recombinant proteins in vaccinia virus systems. 853 47

To increase the efficiency of association of tumor necrosis factor (TNF), a hydrophilic model protein, with liposomes, an N-myristoylation signal sequence was linked to the N-terminus of TNF by gene fusion. A DNA sequence coding for the N-myristoylation signal of Rasheed leukemia virus-gag protein was fused to be 5'-end of the cDNA coding for the mature domain of TNF to give N-myristoylated fusion TNF cDNA. In vitro translation of the mRNA coding for this fusion cDNA using rabbit reticulocyte lysate gave rise to an N-myristoylated fusion TNF with a molecular mass of 18 kDa as determined by the incorporation of [3H]myristic acid and by immunoprecipitation with anti-TNF antibody. Replacement of Gly2 in the myristoylation signal with Ala entirely inhibited the incorporation of [3H]-myristic acid into the fusion protein. A liposome binding assay using Ficoll density gradient centrifugation revealed that incubating the N-myristoylated fusion TNF with dipalmitoyl phosphatidylcholine-liposomes caused the complete binding of the protein to the liposomes, whereas much less of the nonmyristoylated counterpart bound. Thus, N-myristoylated fusion TNF, with high affinity for liposomes, was synthesized by the in vitro translation/transcription system.
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PMID:In vitro synthesis of an N-myristoylated fusion protein that binds to the liposomal surface. 861 Oct 21

Transgenic (TG) mice were generated selectively expressing the gag protein of Friend murine leukemia virus (FMuLV) in the liver. FMuLV(gag) is also expressed by the FBL leukemia, and is the immunodominant tumor Ag of the CD8(+) T cell response in C57BL/6 mice. gag-TG mice expressing FMuLV(gag) in the liver were tolerant to the protein and failed to generate a CTL response to either FBL or FMuLV(gag). This tolerance reflected anergy rather than deletion, as CTL responsiveness could be recovered after four cycles of in vitro stimulation. Adoptively transferred gag-specific T cells were not anergized in gag-TG recipients, as revealed by antitumor activity in vivo. Also, such T cells did not induce detectable autoimmune injury in gag-TG liver cells. These results suggest that the requirements for a tissue Ag to provide a tolerizing stimulus are distinct from those for being the target of a T cell-mediated autoimmune response and that the requirements for induction and maintenance of peripheral tolerance are distinct for naive and primed T cells. That anergic T cells reactive with tumor-associated Ags can be recovered by repetitive in vitro stimulation and can mediate tumor therapy suggests strategies that use such Ags to generate CTL for adoptive immunotherapy should be further developed.
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PMID:Expression of a tolerizing tumor antigen in peripheral tissue does not preclude recovery of high-affinity CD8+ T cells or CTL immunotherapy of tumors expressing the antigen. 1116 Mar 55


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