Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tumor necrosis factor-alpha (TNF-alpha) induces the expression of human immunodeficiency virus type-1 (HIV-1) in vitro in chronically infected cells of T and monocytic origin. The tat protein from the HIV-1 virus has been shown to be essential for HIV replication and in the immunosuppression associated with the virus infection. Previous studies in our laboratory have shown that HIV-1 tat gene induces TNF-beta (lymphotoxin) in human B-lymphoblastoid cells (Sastry et al., 1990, J. Biol. Chem. 265, 20091-20093). In an attempt to characterize further the relationship between the host and HIV-1, we investigated the effect of the functional HIV-1 tat gene on the expression of TNF receptors in a human B lymphoblastoid cell line (Raji). We report here that Raji cells transfected with HIV-1 tat gene express fewer cell surface TNF receptors than control cells. At least a 5-fold decrease in the receptor number without any significant change in receptor affinity was observed. The decrease in TNF receptors in tat-transfected Raji cells (Raji-tat cells) was found not to be due to receptor occupancy by the autocrine production of TNF-beta. The decrease in the cell surface expression of TNF receptors in Raji-tat cells was also found to be not due to a decrease in the gene expression of the receptor. The kinetics, amount of TNF binding and its internalization were temperature dependent, and it was different in Raji-tat cells than in the control cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Down-modulation of cell surface expression of p80 form of the tumor necrosis factor receptor by human immunodeficiency virus-1 tat gene. 133 62

Nef protein, encoded by the regulatory nef gene of human immunodeficiency virus type 1 (HIV-1), was expressed in the B-cell line Raji. The cells were stably transfected with plasmids containing the nef transcriptional cassette. They expressed Nef with an Mr of 27,000; the yield could be augmented by incubation with the tumor promoter 12-O-tetradecanoylphorbol-13-acetate. The intracellular localization of Nef was analyzed applying immunofluorescence microscopy using a confocal laser scanning microscope. The antigen was stained with a monoclonal antibody directed against the N-terminal part of Nef. The experiments revealed that in non-dividing cells Nef is present both in the cytoplasm and the nucleus while in dividing cells the viral protein is present in the cytoplasm and at the nuclear membrane.
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PMID:Expression and cellular localization of the Nef protein from human immunodeficiency virus-1 in stably transfected B-cells. 157 Oct 13

The human immunodeficiency virus type I (HIV-1) regulatory gene, tat III, is a powerful trans-activator of gene expression from the viral long terminal repeat and is essential for HIV replication. In addition, tat III protein has been shown to be immunosuppressive as indicated by the inhibition of antigen mediated T-cell proliferation. To further test whether tat III might play a direct role in the immunosuppressive effects of HIV-1 in addition to its role in virus replication, we examined the regulation of interleukin 4 (IL-4) receptors on a human B-lymphoblastoid cell line (Raji) transfected with HIV-1 tat gene (Raji-tat III). We used radioligand receptor binding analysis for cell surface expression and Northern blot analysis for the expression of human IL-4 receptor gene in Raji-tat III cells. Control Raji cells expressed 1383 +/- 361 (SE; n = 3) IL-4 binding sites/cell with a dissociation constant (Kd) of 144 +/- 27 pM (n = 3). However, Raji-tat III cells expressed about three times higher IL-4 receptors (4000 +/- 633 IL-4 binding sites/cell; P less than 0.03 compared to Raji cells) with a similar Kd of 273 +/- 90 pM (n = 3; P greater than 0.05 compared to Raji cells). Whereas both Raji and Raji-tat III cells exhibited a single mRNA species (approximately 4 kilobases) of IL-4 receptors by Northern blot analysis, the mRNA level was about 3-fold higher in Raji-tat III cells compared to Raji cells. Cycloheximide inhibited the expression of IL-4 receptors by 50% in about 2 h in both cell types indicating both the half-life of IL-4 receptors and the requirement for protein synthesis for the tat III up-regulation of IL-4 receptors. Since IL-4 under certain circumstances has been shown to be immunosuppressant, our observation that the HIV-1 tat gene up-regulates IL-4 receptors suggests the possibility that the immunosuppressive effects of HIV-1 are mediated at least in part through IL-4 receptors.
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PMID:Human immunodeficiency virus type 1 tat gene up-regulates interleukin 4 receptors on a human B-lymphoblastoid cell line. 161 47

We searched for Epstein-Barr virus (EBV) sequences by enzymatic DNA amplification in nine primary brain lymphomas from patients without immunodeficiency. We used seven nonlymphoma brain tumors as negative controls, and the Raji cell line as a positive control. We detected EBV DNA, using ethidium bromide-stained-agarose minigel electrophoresis and dot blot hybridization, in the positive control and in only one brain lymphoma tumor; we did not detect EBV DNA in the other tumors. The EBV-positive patient had a second B-cell monoclonal population in the peripheral blood without detectable EBV DNA, suggesting a direct role for EBV in the development of the brain lymphoma.
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PMID:Detection of Epstein-Barr virus sequences in primary brain lymphoma without immunodeficiency. 164 83

6.1.6 is one of several immunoselected mutants from EBV-transformed human B cell lines that have undergone coordinate loss of expression of all their HLA class II genes. Similar defects have been found in cells from some patients with class II immunodeficiencies. Previous studies have suggested that the defects in 6.1.6 and in the other class II regulatory mutants are in transactive factors required for class II transcription. The defective factors, however, have not been identified. Here we present two lines of evidence that serve to localize the site of action of the factor that is defective in 6.1.6. First, transfected indicator genes linked to HLA DRA promoter fragments that include the conserved X box region are transiently expressed at greatly reduced levels in 6.1.6, compared with the progenitor cell line T5-1. Second, a DNA-protein complex, termed X-A, formed by nuclear extracts from T5-1 with DRA sequences containing the X box and a few bases 5' and 3' to it, is missing with extracts from 6.1.6. Extracts from some but not all patients with class II-negative immunodeficiency also fail to form X-A, whereas extracts from class II-negative mutants derived from the Burkitt's line Raji do form an apparently normal X-A complex. The X-A complex contains proteins of approximately 22, 32, 82, and 92 kDa that can be cross-linked to a 5-bromodeoxyuridine-substituted X box probe by UV light. A defect in an X box-binding protein, or in a factor required for its binding, is a likely cause for the loss of transcription of the class II genes in 6.1.6.
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PMID:Defective HLA DRA X box binding in the class II transactive transcription factor mutant 6.1.6 and in cell lines from class II immunodeficient patients. 190 83

We have reported previously the enhancement of the infectivity of human immunodeficiency virus type 1 (HIV-1) by liposomes composed of the cationic lipid N-[2,3-(dioleyloxy) propyl]-N,N,N-trimethylammonium chloride (DOTMA). To determine the mechanism by which this process occurs, we have investigated the role of CD4, serum concentration and liposome-cell interactions in the DOTMA-mediated stimulation of HIV-1 infection of A3.01 cells. Serum alone significantly inhibited the binding and infectivity of HIV-1, but DOTMA-mediated enhancement of infectivity was more pronounced in the presence of serum than in its absence. HIV-1 binding to cells was increased in the presence of DOTMA liposomes, DEAE-dextran and polybrene, all of which also enhanced infectivity to a similar extent at comparable concentrations. Fluorescence dequenching measurements indicated that DOTMA liposomes fused with HIV-1, but not with cell membranes, in the presence of serum. The enhancing effect of DOTMA liposomes on HIV-1 infectivity was CD4-dependent, and appeared to involve virus-liposome fusion and liposome binding to the cell surface. DOTMA liposomes did not mediate infection of the CD4-K562 and Raji cell lines.
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PMID:Enhancement of human immunodeficiency virus type 1 infection by cationic liposomes: the role of CD4, serum and liposome-cell interactions. 194 Aug 66

Circulating immune complexes (CIC) were analyzed in a cohort of 30 children infected with the human immunodeficiency virus. Elevated CIC were detected by the C1q assay in 70% (21/30) of all patients and by the Raji cell assay in 93% (28/30) of all patients. While only less than one third of patients with elevated CIC had free serum antibodies to Epstein-Barr virus, 80% (16/20) of them had detectable antibodies to Epstein-Barr virus associated with CIC. Enriched CIC in human immunodeficiency virus-infected children contained low levels of complement. These findings document that, as an expression of the humoral immunodeficiency, CIC in human immunodeficiency virus-infected children are deficient in complement and can thus be underestimated if complement-precipitating methods are used for their detection.
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PMID:Immune complexes in pediatric human immunodeficiency virus infection. 217

The tat protein from human immunodeficiency virus type 1 (HIV-1) activates viral gene expression and is essential for HIV replication in vitro. It has also been shown that the tat gene product specifically inhibits antigen-induced proliferation of human peripheral blood lymphocytes. In order to understand the growth and immunomodulatory roles of HIV-1 tat, we have examined the effect of the tat gene on the expression of tumor necrosis factors in a human B-lymphoblastoid cell line (Raji). We report here that the HIV-1 tat gene introduced into Raji cells by retroviral-mediated transformation induces production of tumor necrosis factor-beta (TNF-beta). The tat-mediated induction of TNF-beta seems to be both at the transcriptional and post-transcriptional levels because, concurrent with a 30-fold increase in the levels of TNF-beta protein, an approximate 8-fold increase in mRNA was observed in tat-transformed Raji cells. It is recently reported that tat protein of HIV-1 stimulates growth of cells derived from Kaposi's sarcoma lesions of AIDS patients (Ensoli, B., Barillari, G., Salahuddin, S.Z., Gallo, R.C., and Wong-Staal, F. (1990) Nature 345, 84-86). Since TNF has been shown to function as a growth factor for several cell types, our results showing induction of TNF-beta by tat indicate the possibility that a growth-stimulatory role of HIV-1 tat on Kaposi's sarcoma cells is mediated through TNF-beta.
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PMID:HIV-1 tat gene induces tumor necrosis factor-beta (lymphotoxin) in a human B-lymphoblastoid cell line. 224 81

3'-Azido-2',3'-dideoxythymidine (AZT) and 2',3'-didehydro-2',3'-dideoxythymidine (D4T) are potent and selective inhibitors of human immunodeficiency virus replication in MT-4 and ATH8 cells. They are also inhibitory to the replication of murine retroviruses, i.e. Moloney murine sarcoma virus-induced transformation of C3H cells. In MT-4 cells AZT is readily phosphorylated to its 5'-monophosphate, while the 5'-di- and 5'-triphosphates are generated to a 200-600-fold lower extent than the 5'-monophosphate. D4T is phosphorylated in MT-4 cells to its 5'-monophosphate at a 300-600-fold lower extent than AZT. The phosphorylation of AZT in the thymidine kinase-deficient cell line (Raji/TK-) is severely depressed, while D4T phosphorylation is only slightly diminished in Raji/TK- as compared to Raji/0 cells. D4T has a 10-fold lower affinity for phosphorylation by crude MT-4 cell extracts than AZT (Km, 142 and 14 microM, respectively), and the Vmax for phosphorylation of D4T is only 5% that of AZT. D4T is phosphorylated by MT-4 cell extracts about 180-fold less efficiently than AZT (Vmax/Km, 0.06 for D4T, as compared to 11 for AZT), and this is consistent with the differences found in the amounts of phosphorylated products of D4T and AZT formed in intact MT-4 cells. The 5'-triphosphates of AZT and D4T are equipotent in their inhibitory effects on the reverse transcriptases from human immunodeficiency virus and Moloney murine leukemia virus.
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PMID:Differential patterns of intracellular metabolism of 2',3'-didehydro-2',3'-dideoxythymidine and 3'-azido-2',3'-dideoxythymidine, two potent anti-human immunodeficiency virus compounds. 253 71

Testing of cytotoxic function using a panel of natural killer (NK)-sensitive target cells, including a unique herpes simplex virus-infected Raji-cell target, was performed in conjunction with phenotypic cell analysis by dual-color flow cytometry to characterize the NK system. Subjects included in the study were at risk for or infected with the etiologic agent of the acquired immune deficiency syndrome (AIDS), human immunodeficiency virus (HIV). A generalized defect in NK function was temporally correlated with disease manifestations, as evidenced by deficient NK lytic function in patients with AIDS and AIDS-related complex (ARC). Healthy at-risk subjects, including those seropositive for HIV, exhibited robust NK-cell function. Phenotypic analysis revealed that normal proportions of the NK-associated CD16+ (Leu11) Leu7- and CD16+(Leu11)Leu7+ lymphocyte subsets were maintained throughout the clinical progression of HIV infection. However, the proportion and numbers of cells of the CD8+(Leu2)Leu7+ subset were increased in AIDS, ARC, and healthy at-risk subjects, including those seronegative for HIV. These results are consistent with a qualitative defect in the NK system in AIDS, perhaps secondary to CD4-cell depletion and a concomitant lack of essential accessory factors. The elevation in CD8+(Leu2)/Leu7+ cells is not solely the result of HIV infection and may be a general response to viruses and/or other antigenic stimulation.
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PMID:Alterations in cytotoxic and phenotypic subsets of natural killer cells in acquired immune deficiency syndrome (AIDS). 310 90


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