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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lymphocytes infected in vivo with HIV or lymphoblastoid cells exposed in vitro to either HIV or its envelope glycoprotein (gp120) show a defect in inositol polyphosphate-mediated signal transduction together with an associated abnormality in intracellular calcium regulation. The defect in patients reverses after treatment with the anti-retroviral agent zidovudine (AZT). We present evidence that the defect is at the level of the Ins (1,3,4,5)P4 5-phosphomonoesterase (PME) in these cells and that, though elevation of the intracellular ATP level partially down-regulates the activity of this enzyme, such changes alone are unable to account for the complete inhibition seen in HIV-infected cells.
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PMID:The defect seen in the phosphatidylinositol hydrolysis pathway in HIV-infected lymphocytes and lymphoblastoid cells is due to inhibition of the inositol 1,4,5-trisphosphate 1,3,4,5-tetrakisphosphate 5-phosphomonoesterase. 132 Oct 14

The ability of HIV-1 envelope glycoprotein gp120 to induce transmembrane signaling processes in human T cells and tumor T-cell lines was investigated. Differently glycosylated gp120 preparations were characterized with respect to their purity, the fraction of native gp120, and the affinity of the gp120-CD4 interaction. These data were used to establish experimental conditions that allow a substantial fraction of the CD4 receptor to be complexed with gp120 in the course of the experiments. The results are in contrast to several previous studies since no effect of gp120 on the intracellular Ca2+ concentration, the metabolism of inositol phosphates and arachidonic acid, protein kinase C translocation, and tyrosine phosphorylation was found. Cross-linking of the gp120:CD4 complex by anti-gp120 antibodies did not elicit additional effects.
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PMID:The HIV-1 surface protein gp120 has no effect on transmembrane signal transduction in T cells. 132 56

Human immunodeficiency virus (HIV-1) infection in the human brain leads to characteristic neuropathological changes, which may result indirectly from interactions of the envelope glycoprotein gp120 with neurons and/or glial cells. We therefore investigated the binding of recombinant gp120 (rgp120) to human neural cells and its effect on intracellular signalling. Here we present evidence that rgp120, besides binding to galactocerebroside or galactosyl-sulfatide, specifically binds to a protein receptor of a relative molecular mass of approximately 180,000 Da (180 kDa) present on the CD4-negative glioma cells D-54, but not on Molt4 T lymphocytes. Binding of rgp120 to this receptor rapidly induced a tyrosine-specific protein kinase activity leading to tyrosine phosphorylation of 130- and 115-kDa proteins. The concentration of intracellular calcium was not affected by rgp120 in these cells. Our data suggest a novel signal transducing HIV-1 gp120 receptor on CD4-negative glial cells, which may contribute to the neuropathological changes observed in HIV-1-infected brains.
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PMID:HIV-1 gp120 receptor on CD4-negative brain cells activates a tyrosine kinase. 136 Jan 81

We have examined the biologic activities of native and recombinant preparations of human immunodeficiency virus envelope glycoprotein (gp120), both derived from the HIV-1B strain. Antibody to gp120 was used to evaluate the effects of crosslinking gp120 on signalling by the CD4 receptor. Our results indicate that native and recombinant gp120 produce identical effects in our assay systems. Crosslinking gp120 amplified its chemoattractant activity for lymphocytes and monocytes and increased the peak intracellular calcium level, compared with binding of gp120 alone. The induction of inositol trisphosphate (IP3) production, induction of interleukin 2 receptors (IL2R), and inhibition of lymphocyte proliferation following treatment with gp120 were not enhanced by the addition of crosslinking antibody.
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PMID:Biologic activities of HIV-1 envelope glycoprotein: the effects of crosslinking. 136 93

While expression of complement receptor 2 (CR2) (CD21) on some CD4+ cell lines renders them more susceptible to infection by complement-treated human immunodeficiency virus (HIV), coexpression of CR2 and CD4 on peripheral blood lymphocytes has not, until recently, been observed. Several recent studies, however, have found that human T lymphocytes express low levels of CR2. Additionally, complement treatment of HIV before addition to these cells has been reported to increase virus expression in peripheral blood lymphocyte cultures. These findings suggest that complement-mediated enhancement of infection of human T cells could occur in vivo and have prompted us to examine both the phenotypic properties of CD4+CR2+ T cells in healthy persons and the expression of CR2 on CD4+ lymphocytes during HIV infection. As was previously reported, we observed CR2 on a proportion (10-50%) of both CD8+ and CD4+ T cells. Approximately half of CD4+CR2+ cells expressed the memory cell markers CD45RO and CD29, 80% expressed the naive marker CD45RA, while 22% expressed CD25. These values were not substantially different from total CD4+ cells. Stimulation of lymphocytes with phytohaemagglutinin (PHA), OKT3 or calcium ionophore but not with phorbol myristate acetate (PMA) or interleukin-2 (IL-2) decreased expression of CR2 on CD4 cells by half over a 3-day culture period. The per cent of CD4+ cells expressing CR2 was significantly decreased in patients with asymptomatic and symptomatic HIV infection compared to uninfected control donors (P = 0.0001). In contrast, the decrease in CR2 expression was not observed with CD8+ lymphocytes from HIV-infected persons. These results confirm that CR2 is expressed on human T lymphocytes and suggest that a subset of CD4+ lymphocytes is selectively affected in HIV-infected individuals.
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PMID:Phenotypic analysis of complement receptor 2+ T lymphocytes: reduced expression on CD4+ cells in HIV-infected persons. 137 93

The interference of reverse transcription by heparin was removed by heparinase. When the HIV-1 RNA in the presence of heparin was detected by a combination of reverse transcription and the polymerase chain reaction (PCR), heparinase treatment followed by removal of Ca2+ before the reverse transcription step permitted the efficient detection of HIV-1 RNA. Prior treatment with heparinase revealed HIV-1 RNA in 68% (13/19) of heparinized plasma samples from HIV-1 carriers, whereas only 26% (5/19) of the same specimens were positive without the heparinase step. Heparinase removed the inhibition of reverse transcription by heparin and is highly recommended when detecting low levels of viral RNA in heparinized plasma.
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PMID:Detection of HIV-1 RNA in heparinized plasma of HIV-1 seropositive individuals. 137 11

As many as two-thirds of patients with acquired immunodeficiency syndrome (AIDS) eventually suffer from neurological manifestations, including dysfunction of cognition, movement and sensation. How can human immunodeficiency virus type 1 (HIV-1) result in neuronal damage if neurons themselves are not infected by the virus? In this article Stuart Lipton reviews a series of experiments from several different laboratories that offer related hypotheses accounting for neurotoxicity in the brains of AIDS patients. There is growing support for the existence of HIV- or immune-related toxins that directly or indirectly lead to the injury or demise of neurons via a potentially complex web of interactions between macrophages (or microglia), astrocytes and neurons. However, a final common pathway for neuronal susceptibility appears to be operative, similar to that observed after stroke, trauma and epilepsy. This mechanism involves voltage-dependent Ca2+ channels and NMDA receptor-operated channels, and therefore offers hope for future pharmacological intervention.
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PMID:Models of neuronal injury in AIDS: another role for the NMDA receptor? 138 Nov 20

The cell-surface Ag CD4, which is characteristic for Th lymphocytes, can also be found with a lower density on monocytes/macrophages. Co-cross-linking of CD4 and Fc gamma R by an anti-CD4 mAb (MAX.16H5) and by excess of goat anti-mouse Ig induced a biphasic increase of the free cytosolic Ca(2+)-concentration ([Ca2+]i) in the human monocytoid cell line U937 as measured by FURA-2 fluorescence. A rapid rise from 100 to 150 nM [Ca2+]i to 750 to 900 nM within 1 min was followed by a decline to about 200 to 300 nM within the next 2 to 3 min. This kinetic is characteristic also for blood monocytes and differs significantly from CD4-mediated Ca(2+)-mobilization in T lymphocytes. The rise in [Ca2+]i in U937 cells was not observed when F(ab)2 fragments of MAX.16H5 and F(ab)2 fragments of the cross-linker were used indicating the involvement of Fc gamma R. Time course analysis using HPLC and a recently developed post-column dye system for mass analysis revealed a complex inositol polyphosphate response with rapid increases not only in inositol 1,4,5-trisphosphate and inositol 1,3,4,5-tetrakisphosphate, but also in D/L-inositol 1,4,5,6-tetrakisphosphate, inositol 1,3,4,5,6-pentakisphosphate, and inositol hexakisphosphate after co-cross-linking of CD4 and Fc gamma R. In conclusion, co-cross-linking of CD4 and Fc gamma R, which may occur in vivo during HIV infection or treatment with therapeutic anti-CD4 antibodies, appears to be a strong activation mechanism for the inositol polyphosphate/Ca2+ signal transduction pathway in U937 cells.
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PMID:Complex inositol polyphosphate response induced by co-cross-linking of CD4 and Fc gamma receptors in the human monocytoid cell line U937. 138 92

HIV-1-related neuronal injury may involve a complex web of viral proteins and cytokines, but neurons themselves are not infected. The HIV envelope protein gp120 has been shown to engender an early increase in neuronal free calcium followed by delayed excitotoxic-like damage, which is prevented by N-methyl-D-aspartate (NMDA) antagonists. In the present study, we found that the injurious effects of gp120 on retinal ganglion cell neurons require the presence of macrophages in mixed neuronal glial cultures of postnatal retina. Within 24 hours of incubation, 20 pM gp120 injured nearly 40% of retinal ganglion cells in cultures containing macrophages and other glial cells, whereas no deleterious effects of gp120 were noted on retinal ganglion cells in cultures depleted of macrophages. Thus, the toxic effect of gp120 on neurons appears to be an indirect one, mediated by activation of macrophages and perhaps other glial cells.
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PMID:Requirement for macrophages in neuronal injury induced by HIV envelope protein gp120. 142 Oct 98

Treatment of single rat hippocampal neurons with 200 pM recombinant HIV-1 envelope glycoprotein, gp120, resulted in large increases in the intracellular free calcium concentration ([Ca2+]i) as measured with indo-1-based microfluorimetry. Three patterns of [Ca2+]i increases were observed: in one pattern the [Ca2+]i rose rapidly and transiently as a single peak, in a second pattern gp120 induced [Ca2+]i oscillations that subsided when the protein was removed, and in a third pattern the oscillations continued long after washout of gp120. Both single peak and oscillatory [Ca2+]i increases were completely blocked by the Ca2+ channel blocker nitrendipine (1 microM). The sustained oscillatory responses were also blocked completely and reversibly by the N-methyl-D-aspartate (NMDA) receptor antagonist CGS19755 (10 microM) and the Na+ channel blocker tetrodotoxin (1 microM). Complete block by antagonists of Ca2+, Na+, and NMDA-gated ion channels suggests that at least two cells are required to maintain the [Ca2+]i oscillations. We hypothesize that gp120 acts as an excitotoxin by increasing synaptic activity in the network of neurons established in primary culture.
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PMID:HIV-1 envelope protein evokes intracellular calcium oscillations in rat hippocampal neurons. 145 Sep 45


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