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 effects of oxygen deprivation, or anoxia, on human immunodeficiency virus (HIV-1) expression in chronically (ACH.2) and acutely (H9/HIV-1-IIIB) infected cell lines was investigated. Temporary cellular anoxia has previously been shown to activate transcription of endogenous type C leukemia virus sequences, resulting in a significant increase in retroviral RNA within the cell (1). Here we report a 15-fold increase in HIV-1-specific RNA in unstimulated ACH.2 T cells within 24 h of anoxia. This induction of RNA is accompanied by an accumulation of intracellular p24 gag protein as well as an increase in envelope protein. Anoxia induces a further increase in total HIV-1 RNA in ACH.2 cells prestimulated to produce virus by phorbol 12-myristate 13-acetate and in H9 T cells acutely infected with HIV-1-IIIB. The induction of RNA in ACH.2 cells appears to be reversible. Anoxic culture for 24 h followed by a 24-h re-oxygenation period results in a return to "resting state" levels of HIV-1 RNA. These data indicate that oxygen tension within the cellular environment modulates HIV-1 expression, providing a model system in which to study the reversible regulation of HIV-1 RNA and viral gene products within the cell.
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PMID:Anoxia induces human immunodeficiency virus expression in infected T cell lines. 190 63

A panel of newly isolated monoclonal antibodies (MoAbs) is described which are specific for bovine leukaemia virus (BLV) envelope protein gp51. Epitope mapping using competition antibody binding assays and binding studies with gp51-related fusion proteins and synthetic peptides show that they are directed against seven independent antigenic determinants. Four of them are unrelated to the epitopes described earlier (Bruck et al., 1982a). We define three binding regions for the MoAbs on the gp51 molecule. The region between amino acids 170 and 217 is highly immunogenic when the isolated protein is used for immunization, and seems to be inaccessible for immune recognition when gp51 is associated with the virus envelope as it occurs during natural BLV infection.
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PMID:Identification of an immunodominant region on the isolated bovine leukaemia virus (BLV) major envelope protein gp51 by monoclonal antibodies presumably not exposed during natural BLV infection. 198 Mar 98

(B10.A x A/WySn)F1, H-2a/a, mice are genetic nonresponders to the envelope protein of Friend murine leukemia helper virus (F-MuLV) when immunized with a recombinant vaccinia virus expressing F-MuLV env gene. In contrast these mice can be protectively immunized against leukemogenic Friend virus complex using formalin-fixed F-MuLV virions in CFA. To determine which viral proteins were responsible for this immune protection, virion proteins prepared by SDS-PAGE and electroelution were used to immunize mice. Purified gp70 envelope protein in CFA was capable of inducing strong immune protection against the challenge with Friend virus complex in H-2a/a mice. Immunologic studies demonstrated that immunized mice developed a virus-specific T cell proliferative response and showed IgM to IgG Ig class switching of virus-neutralizing antibodies. These results indicated that genetically controlled immune nonresponsiveness to F-MuLV envelope Ag in H-2a/a mice could be overcome using denatured viral envelope protein together with a strong adjuvant.
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PMID:Induction of protective immunity to Friend murine leukemia virus in genetic nonresponders to virus envelope protein. 203 65

The regulator of virion protein expression (Rex) of the human T-cell leukemia virus type I (HTLV-I) modulates the pattern and level of spliced and unspliced retroviral mRNA species in the cytoplasm. The elucidation of the molecular basis for this regulation is likely to throw light on new regulatory mechanisms of the host cell. We have investigated the possibility that Rex acts to direct unspliced viral RNA to the nucleolus. To test this possibility, we used in situ hybridization to detect HTLV-I envelope protein (env) transcripts formed in the nucleolus in the presence and absence of the Rex protein. The HTLV-I env sequences are normally removed by splicing from the HTLV-I RNA in the absence of Rex. The experiments presented here show that the accumulation of HTLV-I env sequences in the nucleolus is significantly increased in the presence of Rex. The results raise the possibility that Rex directs unspliced viral mRNA to the nucleolus whence it is exported to the cytoplasm for translation. The association between the nucleolus and retroviral mRNA was lost in purified nucleoli after cellular fractionation.
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PMID:Rex-dependent nucleolar accumulation of HTLV-I mRNAs. 206 24

The envelope protein of the human T-cell leukemia virus type I (HTLV-I) is highly conserved among the isolates sequenced so far, as opposed to what is observed for the human immunodeficiency virus (HIV) envelope. By linker insertion scanning, we have produced 33 random mutations along the HTLV-I envelope gene, cloned into a eukaryotic expression vector. The resulting envelope products were analysed by immunoprecipitation and syncytia formation after transfection into COS-1 cells. We show here that 25 out of 33 mutations result in a non-functional envelope product as assessed by the lack of ability to form syncytia. In the majority of these mutants, the processing of the envelope gp61 precursor into the mature gp45 and gp20 proteins was affected. We propose that conformational constraints for processing and fusion abilities tend to limit the variability of the HTLV-I envelope. In three mutants, processing was observed but no syncytia were formed. These mutations might affect regions important for HTLV-I envelope functions, such as the receptor binding region.
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PMID:Mutations introduced along the HTLV-I envelope gene result in a non-functional protein: a basis for envelope conservation? 212 68

Heterogeneity in the structure of the envelope proteins has been observed in many human and animal retroviruses and may influence pathogenicity. However, the biological significance of this heterogeneity and the mechanisms by which it is generated are poorly understood. We have studied a mouse model in which the envelope gene structure of lymphoma-associated viruses appears to be controlled by a single host gene. The inoculation of HRS and CWD mice with a leukemogenic murine leukemia virus (MuLV) results in recombination between the injected virus and envelope gene sequences of endogenous retroviruses. The genomes of HRS (class I) env recombinants and CWD (class II) env recombinants differ in the sequences encoding the NH2-terminal portion of the transmembrane envelope protein (TM). We have shown that an HRS gene linked to the MHC on chromosome 17 mediates a dominant selection for recombinant retroviruses with the class I envelope gene structure. CBA mice, which share the H-2k haplotype with HRS, also carry the dominant allele at this locus. This system provides a useful model for studies of host factors involved in the selection of specific variants of pathogenic retroviruses.
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PMID:A host gene regulates the structure of the transmembrane envelope protein of murine leukemia viruses. 215 51

A highly specific monoclonal antibody (mAb) directed against envelope protein gp51 and effectively bonding the antigen (Ag) on account of its high affinity from an unpurified Ag preparation was chosen for use in a double-sandwich enzyme immuno-assay (EIA) for diagnosis of bovine leukaemia virus (BLV). The epitopes recognised in bovine sera by the gp51-specific antibodies were at the same time properly exposed. Some parameters of major importance to testing were optimised (Ab and Ag quantities, dilution of bovine sera for testing). Preliminary testing of the double-sandwich EIA on selected bovine sera and comparison with both the immunodiffusion test and anti-BLV EIA confirmed its good diagnostic specificity and sensitivity. Hence, this double-sandwich EIA, developed by means of an mAB against gp51, on account of the possibility to use as Ag culture supernatant of the FLC cell line, is a sensitive, low-cost alternative to the anti-BLV EIA Dessau MTP which had so far been used. The double-sandwich EIA is recommended for use in final sanitation for its high analytical and diagnostic sensitivity.
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PMID:[Use of a monoclonal antibody against envelope protein gp51 of bovine leukemia virus in a test for the diagnosis of enzootic bovine leukosis]. 216 49

The CasBrE strain of neurotropic ecotropic murine leukemia virus (NE-MuLV) infects susceptible mice and induces a noninflammatory, slowly degenerative nervous system disease. We employed immunohistochemistry to identify which cells in the nervous system and other tissues contained viral antigen in the chronically infected mouse. Rabbit antiserum to the virus was prepared using different combinations of whole virus and synthetic peptides corresponding to a 14-amino-acid sequence of the viral envelope protein. Twenty-four of forty-four (55%) mice neonates inoculated intracranially with NE-MuLV developed symptoms ranging from tremulousness to hindlimb paralysis within 3-9 months. They were subsequently sacrificed and their tissues used for histology and immunohistochemistry. The major locations of viral antigen outside of the central nervous system (CNS) were skeletal muscle and spleen. Skeletal muscle was the only non-nervous system tissue that exhibited degenerative changes as atrophy of viral antigen-bearing oxidative myofibers. In the CNS, viral antigen was detected in neurons, endothelium, and glial cells. Immunohistochemical double-labeling studies for viral antigen and the astrocytic marker glial acidic fibrillary protein (GFAP) demonstrated that the viral antigen-containing glia were oligodendrocytes and not astrocytes. Tissue damage in the brain consisted of vacuolar changes and gliosis principally in the brainstem. Viral antigen was most abundantly localized in these regions of pathologic change. In the spinal cord a different pattern was observed. Although tissue damage was observed throughout the cord, viral antigen was located at the border of the gray and white matter. These findings indicate direct and indirect virus-mediated mechanisms of damage to the CNS.
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PMID:Immunohistochemical localization of neurotropic ecotropic murine leukemia virus in moribund mice. 216 45

Visna virus is an ungulate lentivirus that is distantly related to the primate lentiviruses, including human immunodeficiency virus type 1 (HIV-1). Replication of HIV-1 and of other complex primate retroviruses, including human T-cell leukemia virus type I (HTLV-I), requires the expression in trans of a virally encoded post-transcriptional activator of viral structural gene expression termed Rev (HIV-1) or Rex (HTLV-I). We demonstrate that the previously defined L open reading frame of visna virus encodes a protein, here termed Rev-V, that is required for the cytoplasmic expression of the incompletely spliced RNA that encodes the viral envelope protein. Transactivation by Rev-V was shown to require a cis-acting target sequence that coincides with a predicted RNA secondary structure located within the visna virus env gene. However, Rev-V was unable to function by using the structurally similar RNA target sequences previously defined for Rev or Rex and, therefore, displays a distinct sequence specificity. Remarkably, substitution of this visna virus target sequence in place of the HIV-1 Rev response element permitted the Rev-V protein to efficiently rescue the expression of HIV-1 structural proteins, including Gag, from a Rev- proviral clone. These results suggest that the post-transcriptional regulation of viral structural gene expression may be a characteristic feature of complex retroviruses.
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PMID:Visna virus encodes a post-transcriptional regulator of viral structural gene expression. 217 Sep 81

Twenty patients with chronic purulent rhinosinusitis were treated with TP-1 (Serono; 1 mg/kg body weight), in a double-blind cross-over trial. TP-1 was administered by daily i.m. injections for the first 14 days followed by two injections/week for 6 further weeks. The patients were immunologically special in that they had defects in their cell-mediated immune system. Fourteen showed a decreased chemotactic responsiveness of their peripheral blood monocytes as measured in the polarization assay. This defective function can probably be ascribed to the presence in serum of low molecular weight factors (LMWFs; less than 25 kD). As reported earlier, this factor shows a structural homology to the envelope protein of murine and feline leukaemia virus (P15E). Thirteen patients showed a defective delayed-type hypersensitivity (DTH) skin test reactivity towards candidin and/or streptokinase-streptodornase (Sk/Sd) antigen, 14 had a defective MIF production from their peripheral blood lymphocytes towards candidin, Sk/Sd and/or Haemophilus influenzae antigen. Eighteen patients completed the TP-1 trial and showed clinical improvements: 12 out of 15 were feeling better during TP-1 therapy and the nasal mucosa showed on inspection absent mucopurulent secretion in 13 patients. Positive bacterial culture rates for the nose decreased from 14 out of 16 to five out of 15. Placebo treatment had no significant effects. The clinical improvements were accompanied by a better performance of the cell-mediated immune system; the most significant effects were recorded in the monocyte polarization assay. The suppressive P15E-like LMWFs in serum clearly decreased during TP-1 treatment. In vitro TP-1 neutralized the immunosuppressive effect of the LMWFs. The restoring effects of TP-1 on monocyte polarization and its neutralizing activity of P15E-like LMWFs could explain the beneficial effects of thymic hormone treatment reported in adults with clinical signs of immunodeficiency in the presence of a full T cell repertoire.
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PMID:Beneficial effects of the thymic hormone preparation thymostimulin in patients with defects in cell-mediated immunity and chronic purulent rhinosinusitis. A double-blind cross-over trial on improvements in monocyte polarization and clinical effects. 219 46


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