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 determinants critical for the incorporation of Pr160(gag-pol) into human immunodeficiency virus type 1 (HIV-1) particles were examined by cotransfecting cells with (i) a plasmid expressing wild-type Gag protein and (ii) a series of chimeric Gag-Pol expression plasmids in which individual murine leukemia virus (MLV) Gag regions and subdomains precisely replaced their HIV-1 counterparts. The presence of the MLV MA and NC Gag regions in the chimeric Gag-Pol precursor had no detectable effect on the incorporation of Gag-Pol into progeny virions. In contrast, the entire HIV-1 CA region was required to achieve wild-type levels of Gag-Pol assembly into particles; both the CA major homology region and the adjacent C-terminal CA sequences play dominant roles in this process yet, when assayed in the context of a chimeric Gag-Pol polyprotein, restored the defect affecting Gag-Pol incorporation to approximately half of the wild-type level.
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PMID:Incorporation of Pr160(gag-pol) into virus particles requires the presence of both the major homology region and adjacent C-terminal capsid sequences within the Gag-Pol polyprotein. 915 38

The yeast two-hybrid system was used to characterize homomeric interactions between the Gag proteins of Rous sarcoma virus (RSV). The RSV Gag precursor was found to interact strongly with itself and not with various control proteins. The RSV Gag did not interact significantly with Gag proteins of a variety of other retroviruses, including murine leukemia viruses and primate lentiviruses. Deletion analysis suggested that two nonoverlapping regions are independently sufficient to mediate RSV Gag-Gag dimerization. One such region lies near the N terminus and contains p2, p10, and a large N-terminal part of the capsid (CA) domain; the other is localized in the C terminus and includes a small C-terminal portion of CA and the nucleocapsid protein. These interaction domains may play roles in viral assembly.
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PMID:Genetic analysis of interactions between Gag proteins of Rous sarcoma virus. 918 38

We injected with HTLV-1-producing T-cells, MT-2, into C3H/HeJ and Balb/c mice intraperitoneally within 24 hours after birth and at one week old. At 3 months old, HTLV-1 provirus was detected in peripheral blood mononuclear cells in both mice. It was also detected in lymph nodes, thymus, spleen and liver of those mice. The antibody response against HTLV-1 Gag antigen was detected in some of Balb/c mice. These findings suggest that the C3H/HeJ and Balb/c mice were infected with HTLV-1 persistently. The HTLV-1-infected mice should be helpful for studying the pathological state of HTLV-1 carriers and for an establishment of a small animal model of HTLV-1 related diseases including ATL.
Leukemia 1997 Apr
PMID:Establishment of HTLV-1 carrier mice by injection with HTLV-1-producing T cells. 920 59

In an early step in the retroviral infectious process, reverse transcriptase copies the genomic RNA of the virus into complementary minus-strand DNA. The primer for this synthetic event is a molecule of cellular tRNA, which is annealed by its 3' 18 nucleotides to a region of the genomic RNA termed the primer-binding site (PBS); the sequence of the PBS and hence the identity of the tRNA depend upon the retrovirus species. In addition to the primer tRNA, retrovirus particles contain a substantial number of other tRNA molecules. The latter tRNA population is enriched for the tRNA species which serves as primer for the virus. While there is considerable evidence that the enrichment for the primer species can be attributed to the pol gene product, nothing is known regarding mechanisms of annealing the primer to the PBS. We have analyzed pol- mutants of avian leukosis virus (ALV) and murine leukemia virus (MuLV) for the presence of primer at the PBS in virion genomic RNA. Remarkably, the results were different for the two viruses: the PBS was substantially occupied by primer in MuLV but not in ALV. Previous data indicates that the Pol-dependent enrichment of the primer within the virion is much greater in ALV than in MuLV. We therefore propose that the absence of primer at the PBS in pol- ALV is due to the deficiency of the primer species within the particle. The results suggest that, at least in MuLV, the tRNA is unwound by either the Gag protein or a cellular protein for annealing to the PBS. Further, the C-terminal 17 amino acids of Gag are unnecessary for this function in MuLV.
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PMID:Placement of tRNA primer on the primer-binding site requires pol gene expression in avian but not murine retroviruses. 926 22

We have demonstrated that COS7 cells transiently co-expressing myristylation-defective (Myr-) and protease-defective (PR-) human immunodeficiency virus (HIV) mutants can release infectious virions when co-transfected with an amphotropic murine leukaemia virus envelope protein expression plasmid (SV-A-MLV-env). In contrast, no infectious virions were detected when a PR-, noninfectious HIV gag mutant was co-expressed with the Myr- mutant, although the Myr- mutant could still process the immature core particles in trans. This result indicates that generation of functionally normal Gag proteins is required for virus infectivity in our complementation system. A mutant with a 56-amino-acid deletion in the N-terminal region of the capsid (CA) domain could still complement the PR- mutant to generate infectious virions, suggesting that the deletion mutant could provide a functional protease for processing in the PR- mutant. This result is consistent with the concept that mutations within the N-terminal region of the CA domain have no major effects on Gag-Pol incorporation into particles.
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PMID:Generation of infectious virus particles by transient co-expression of human immunodeficiency virus type 1 gag mutants. 934 70

The 96-amino acid protein Vpr functions as a regulator of cellular processes involved in human immunodeficiency virus, type 1 (HIV-1) life cycle, in particular by interrupting cells division in the G2 phase. Incorporation of Vpr in the virion was reported to be mediated by the C-terminal domain of the Pr55(Gag) polyprotein precursor, which includes NCp7, a protein involved in the genomic RNA encapsidation and p6, a protein required for particle budding. To precisely define the Gag and Vpr sequences involved in this protein-protein interaction, NCp7, p6, and Vpr as well as a series of derived peptides were synthesized using Fmoc (N-(9-fluorenyl)methoxycarbonyl) chemistry. Binding assays were carried out by Far Western experiments and by competition studies using (52-96)Vpr immobilized onto agarose beads. The results show that interaction between NCp7 and Vpr occurs in vitro by a recognition mechanism requiring the zinc fingers of NCp7 and the last 16 amino acids of Vpr. Moreover, NCp10, the equivalent of NCp7 in Moloney murine leukemia virus but not polysine inhibits Vpr-NCp7 complexation. Interestingly enough, Vpr was found to interact with Gag, NCp15, and NCp7 but not with mature p6 in vitro. In vivo mutations in NCp7 zinc fingers in an HIV-1 molecular clone led to viruses with important defects in Vpr encapsidation. Together, these results suggest that NCp7 cooperates with p6 to induce Vpr encapsidation in HIV-1 mature particles. The NCp7-Vpr complex could also be important for interaction of Vpr with cellular proteins involved in cell division.
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PMID:The zinc fingers of HIV nucleocapsid protein NCp7 direct interactions with the viral regulatory protein Vpr. 938 14

Interaction of retrovirus vectors and endogenous retroviruses present in packaging cell lines and target cells may result in unwanted events, such as the formation of recombinant viruses and the mobilization of therapeutic vectors. Using sensitive reverse transcriptase PCR assays, we investigated human and murine gene therapy packaging cell lines for incorporation of endogenous retrovirus transcripts into murine leukemia virus (MLV) vector particles and, conversely, whether vector genomes are incorporated into human endogenous retrovirus (HERV) particles. VL30 endogenous retrovirus sequences were efficiently packaged in particles produced by the murine AM12 packaging system. For every seven MLV-derived beta-galactosidase (beta-Gal) vector genomes present in the particles, one copy of VL30 was also packaged. Although human FLY packaging cells expressed several classes of HERV transcripts (HERV-K, HuRT, type C, and RTVL-H), none was detectable in the MLV vector particles released from the cells. Nonspecific packaging of the MLV Gag-Pol expression vector transcripts was detected in the FLY virions at a low level (1 in 17,000 sequences). These findings indicate that human packaging cells produce retrovirus particles far less contaminated by endogenous viral sequences than murine packaging cells. Human teratocarcinoma cells (GH cells), which produce HERV-K particles, were transduced with an MLV-derived beta-Gal vector. Although both HERV-K and RTVL-H sequences were found in association with the particles, beta-Gal transcripts were not detected, indicating that HERV Gag proteins do not efficiently package MLV-based vectors.
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PMID:Packaging of endogenous retroviral sequences in retroviral vectors produced by murine and human packaging cells. 952 84

In this work we have studied the intracellular localization properties of the Gag and Env proteins of Moloney murine leukemia virus (MLV) and human immunodeficiency virus (HIV) in dorsal root ganglion (DRG) neurons of rat. These neurons form thick bundles of axons, which facilitates protein localization studies by immunofluorescence analyses. When such neuron cultures were infected with recombinant Semliki Forest virus particles carrying the gag genes of either retrovirus, the expressed Gag proteins were localized to both the somatic and the axonal regions of the DRG neurons. In contrast, the Env proteins were confined only to the somatic region. When the Gag and Env proteins were coexpressed, the Gag proteins were also excluded from the axons. This effect of the Env proteins was shown to be dependent on the concentration of the Gag proteins in the neuron and also to be specific for homologous pairs of retrovirus proteins. Therefore, the results suggest that there are specific interactions between the Env and the Gag proteins of MLV and HIV in the DRG neurons.
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PMID:Specific interactions between retrovirus Env and Gag proteins in rat neurons. 952 3

Host proteins are incorporated into retroviral virions during assembly and budding. We have examined three retroviruses, human immunodeficiency virus type 1 (HIV-1), simian immunodeficiency virus (SIV), and Moloney murine leukemia virus (Mo-MuLV), for the presence of ubiquitin inside each of these virions. After a protease treatment to remove exterior viral as well as contaminating cellular proteins, the proteins remaining inside the virion were analyzed. The results presented here show that all three virions incorporate ubiquitin molecules at approximately 10% of the level of Gag found in virions. In addition to free ubiquitin, covalent ubiquitin-Gag complexes were detected, isolated, and characterized from all three viruses. Our immunoblot and protein sequencing results on treated virions showed that approximately 2% of either HIV-1 or SIV p6Gag was covalently attached to a single ubiquitin molecule inside the respective virions and that approximately 2 to 5% of the p12Gag in Mo-MuLV virions was monoubiquitinated. These results show that ubiquitination of Gag is conserved among these retroviruses and occurs in the p6Gag portion of the Gag polyprotein, a region that is likely to be involved in assembly and budding.
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PMID:Ubiquitin is covalently attached to the p6Gag proteins of human immunodeficiency virus type 1 and simian immunodeficiency virus and to the p12Gag protein of Moloney murine leukemia virus. 952 17

Replication of Moloney murine leukemia virus requires a readthrough translation mechanism to generate the Gag-Pol polyprotein. One of the final products of this polyprotein is the protease (PR), which is required to generate the mature virion proteins. The assembly of Gag and Gag-Pol polyprotein into a virion followed by activation of the viral protease is necessary to produce a mature, infectious particle. These events are believed to occur near the cell membrane just prior to the budding of the virion. We report here the autoproteolytic activity of the viral PR when a Gag-PR fusion protein is expressed in E. coli. Efficient cleavage at the p12/CA, CA/NC and NC/PR junctions was observed. Thus the Moloney murine leukemia virus PR is capable of cleaving its substrates in the absence of specific host factors.
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PMID:Moloney murine leukemia virus protease expressed in bacteria is enzymatically active. 954 21


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