UMLS:C0019693 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

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

kappa B elements have been described as lymphoid-specific transcriptional activators. Here we show that kappa B elements are able to stimulate expression from test promoters more than 100-fold in T47D and 3T3 non-lymphoid cells. We also demonstrate that nuclear proteins from T47D cells form two prominent complexes with HIV kappa B sites. Since the complexes formed in nuclear extracts from T47D and PHA/PMA stimulated Jurkat cells comigrate in polyacrylamide gels, we suggest that the respective binding protein in T47D cells is either NF-kappa B or a closely related family member. In addition we provide evidence that NF1 and kappa B elements can act synergistically to further increase transcriptional activity.
...
PMID:kappa B elements strongly activate gene expression in non-lymphoid cells and function synergistically with NF1 elements. 251 Jan 29

The relationship of T cell activation to HIV entry and generation of viral DNA intermediates was studied in freshly isolated CD4+ T lymphocytes. Unstimulated cells exposed to infectious virus for up to 48 h did not synthesize any detectable unintegrated HIV DNA duplex forms or integrated genomic provirus. However, activation of these cells with either PHA or OKT3 (anti-CD3) mAb before viral exposure resulted in the generation of unintegrated HIV DNA after 6 h and integrated copies after 24 h. Cell-to-cell fusion studies showed significantly attenuated fusion between freshly isolated resting T cells and T cells constitutively expressing high levels of HIV envelope glycoprotein (HXB/gpt) compared with T cells first stimulated with either PHA or OKT3 mAb. The baseline fusion observed with resting T cells is believed to be a consequence of allogeneic stimulation by the HXB/gpt cell line. These results provide evidence that HIV entry and HIV envelope-dependent cell-to-cell fusion require T cell activation.
...
PMID:Evidence that T cell activation is required for HIV-1 entry in CD4+ lymphocytes. 252 8

Equine infectious anemia (EIA) is a disease caused by a lymphocytotropic lentivirus which belongs to the same subfamily as HIV. Because of the very close relationship of their predicted gag and pol gene products and similarities in clinical manifestations of the disease, EIA served as a model to study immunological events involved in the host defence against lymphocytotropic viral infections. The existence of antibody dependent cell-mediated cytotoxicity against autologous EIA virus infected lymphoblasts was demonstrated in vitro at the beginning of an acute attack of the disease. Cytotoxic activity was not found or was very low during chronic infection. Reactivity of peripheral blood lymphocytes to Protein A and allogeneic cells in vitro was significantly suppressed in the presence of an acute serum, while the reactivity to PHA was at the normal level. These results suggest that cellular immune mechanism(s) are also involved in removal of EIA virus infected cells as has been reported recently in HIV-1 infected individuals and that EIAV and HIV immunopathogenesis show similarities in affecting the immune response of the host.
...
PMID:Qualitative analyses of cellular immune functions in equine infectious anemia show homology with AIDS. 252 15

HIV infection is known to induce a progressive T helper/inducer (CD4) lymphopenia and to impair the functional activities of residual cells. The present studies examined the relationship between the CD4 cell count and three functional assays: T cell colony formation in semisolid media, the capacity of PHA-stimulated cells to express IL-2 receptors, and their ability to synthesize and secrete IL-2. Cells from antibody-positive homosexuals with normal numbers of CD4 cells (greater than 700/microliters) showed defective reactivity in two assays, colony growth, and IL-2 receptor expression. These defects became progressively more pronounced in homosexuals with moderate (400-700 cells/microliters) and severe (less than 400/microliters) reductions in assays for IL-2 production by PHA-stimulated lymphocytes. Mixing experiments suggest that cells from HIV-infected men nonspecifically inhibit the colony growth of normal cells; this abnormality could be reversed by addition of exogenous IL-2. These data suggest that defective colony growth and reduced IL-2 expression are functional abnormalities directly resulting from HIV infection. Furthermore, these changes can precede the CD4 lymphopenia induced by this viral infection.
...
PMID:Defective T cell colony formation and IL-2 receptor expression in HIV-infected homosexuals: relationship between functional abnormalities and CD4 cell numbers. 252 69

The state of T cell activation and proliferation controls HIV-1 replication and gene expression. Previously, we demonstrated that the administration of PHA and PMA to the human T cell line Jurkat activates the HIV-1 enhancer, which is composed of two nuclear factor kappa B (NF kappa B) binding sites. Here, we show that PMA alone is sufficient for this effect. In addition, activation of T cells through the surface proteins TCR/CD3 and CD28 increased gene expression directed by the HIV-1 long terminal repeat (LTR) to the same extent as PMA. Analysis of 5' deletions in the LTR revealed that the NF kappa B binding sites and sequences in the upstream U3 region are required for this response. Whereas cyclosporin A did not inhibit the effect of PMA, it reduced the effects of agonists to TCR/CD3 and CD28 on the LTR. H7, an inhibitor of protein kinase C (PKC), blocked the effects of all stimuli. Thus, PMA activates the NF kappa B sites through a PKC-dependent pathway while ligands to TCR/CD3 and CD28 activate the LTR through a cyclosporin A-sensitive, PKC-dependent pathway of T cell activation. We conclude that mechanisms involved in the expression of IL-2 and the alpha-chain of the IL-2R alpha genes also play a role in the regulation of HIV-1. Physiologic stimuli can activate HIV-1 gene expression; agents that block T cell activation also inhibit activation of the LTR. These observations might serve as a model for the regulation of HIV-1 gene expression in peripheral blood T cells.
...
PMID:Signaling through T lymphocyte surface proteins, TCR/CD3 and CD28, activates the HIV-1 long terminal repeat. 253 62

We studied the proliferative response of PBL to the mitogens PHA and PWM and Candida albicans Ag in 301 HIV seropositive homosexual men, of whom 55 had AIDS. The responses to PHA were reduced only in the clinically ill HIV seropositive subjects. In contrast, the responses to PWM were profoundly reduced in most HIV seropositive subjects including the asymptomatic group. Further analysis of 16 HIV seropositive subjects showed that the proliferative responses were reduced in both CD4 and CD8 T cell subsets. A total of 15 HIV seropositive individuals with low responses to PWM, of whom seven had AIDS and eight controls were chosen for the following studies. Expression of T3, Ti, delta receptors, and CD2 was investigated and showed an increased percentage of CD2 receptors positive cells in HIV seropositive subjects without AIDS. The proliferative responses of PBL to stimulation with PHA, PWM, antibodies to CD3, or antibodies to CD2 were investigated and showed significant correlation in controls, whereas in contrast, only the responses to PHA and CD2ab correlated in patients with AIDS. The proliferative responses to CD2ab and CD3ab in controls were larger than the responses to both PHA and PWM. In patients, these responses were less suppressed than the responses to PWM indicating that stimulation with mitogens is more complex than a simple stimulation of Ti/T3 and CD2 receptors. Further investigations were done on resting T cells, i.e., lymphocytes depleted of macrophages and pre-activated cells. Addition of PHA to these cells resulted in preactivation with expression of IL-2R (CD25) but not in proliferation. In contrast, addition of PHA plus SRBC, which bind to the CD2 receptors caused IL-2R expression, IL-2 production, and proliferation. Addition of PWM + SRBC did not result in proliferation. A comparison of the responses to PHA + SRBC of resting T cells from 26 HIV seropositive individuals, of whom seven had AIDS and 12 seronegative controls, showed that these responses were normal or only slightly decreased in the 19 seropositive men without AIDS whereas it was decreased in AIDS patients. Nevertheless, all AIDS patients showed clear-cut responses in this assay. Thus, the discrepancy between responses to PHA and PWM may be explained by an at least partially preserved function of the PHA/CD2-dependent pathway. We suggest that the defect induced by the HIV infection primarily concerns T3/Ti-induced responses.
...
PMID:HIV-induced immunodeficiency. Relatively preserved phytohemagglutinin as opposed to decreased pokeweed mitogen responses may be due to possibly preserved responses via CD2/phytohemagglutinin pathway. 256 29

We have addressed the capacity of HIV-1 infection to alter the growth of primary CD4+ T cells, but at the clonal level. Single T cells were expanded in the presence of PHA, IL-2, and small numbers of accessory dendritic cells. We report two new findings. First, T cells from seropositive individuals, even those with AIDS and markedly reduced CD4+ counts, exhibit a normal cloning efficiency, and proliferative capacity. This result is in contrast to two prior reports of a low cloning efficiency in CD4+ T cells from HIV-1-infected patients. Second, when we added high doses of exogenous HIV-1 to T cell clones from control subjects, we observed infection but not cytotoxicity or loss of CD4+ cells, following addition of virus stocks at days 0, 3, and/or 7 of clonal growth. The same HIV-1 isolates markedly reduced CD4+ T cells in bulk mononuclear cultures. When tested at day 11, HIV-1 mRNA was expressed in some cells of exogenously infected clones by in situ hybridization; when tested at day 18, several clones could transactivate a TAT-sensitive cell line. These findings suggest that the loss of CD4+ T cells in infected individuals is not the inevitable result of the activation of latent infection, or spread of a productive infection, during clonal growth.
...
PMID:Most CD4+ T cells from human immunodeficiency virus-1 infected patients can undergo prolonged clonal expansion. 257 7

We have tested the T helper cell (TH) potential of asymptomatic, HIV seropositive (HIV+) patients, using an in vitro assay for IL-2 production. Peripheral blood leukocytes (PBL) from 74 HIV+ patients and 70 HIV- control donors were tested for TH function when stimulated with influenza A virus (FLU), tetanus toxoid (TET), HLA alloantigens (ALLO), or PHA. Of the HIV+ patients, four different response patterns were observed: (a) patients who responded to all four stimuli (16%); (b) patients who were selectively unresponsive to FLU and TET, but responded to ALLO and PHA (54%); (c) patients who were unresponsive to FLU, TET, or ALLO, but responsive to PHA (16%); and (d) patients who failed to respond to any of these stimuli (14%). Our results indicate a time-dependent progression from a stage responsive to all four stimuli to a stage unresponsive to any of the stimuli tested, progressing in the order outlined above. The earliest TH defect is the loss of responses to FLU and TET, indicating a selective defect in CD4+ MHC self-restricted TH function. The later loss of ALLO and PHA IL-2 responses suggests more severe TH dysfunction involving both CD4+ and CD8+ T cells. None of these patterns of TH unresponsiveness in asymptomatic HIV+ individuals were correlated with CD4+ cell numbers nor with Walter Reed staging criteria. This study indicates that the in vitro TH assay used can detect multiple stages of immune dysregulation early in the course of HIV infection and raises the possibility that staging of HIV+ patients should include in vitro TH functional analyses of the type described here.
...
PMID:Detection of three distinct patterns of T helper cell dysfunction in asymptomatic, human immunodeficiency virus-seropositive patients. Independence of CD4+ cell numbers and clinical staging. 257 88

We have investigated the effect of TNF, a cytokine produced during most immunologic and inflammatory reactions, on HIV genome expression in human T lymphocytes. A CD4+ human T cell line (J.Jhan) was transfected with vectors permitting the expression of the chloramphenicol acetyl transferase (CAT) gene under the control of the long terminal repeat (LTR) of HIV-1. rTNF was found to induce HIV LTR transactivation as intensely as PHA or phorbol esters. PHA enhanced TNF receptor expression in J.Jhan cells and acted synergistically with TNF on HIV LTR induction. TNF was also shown to induce well expression of a whole HIV provirus genome transfected into J.Jhan cells. The use of various CAT constructs carrying fragments of the HIV LTR, combined with bandshift assays, showed that TNF stimulates HIV transcription by acting on the kB-like enhancer element of the LTR through induction and/or activation of an NF-kB-like protein factor. Such findings are compatible with the hypothesis that TNF production participates in the pathogenesis of AIDS by enhancing HIV replication in T lymphocytes.
...
PMID:Tumor necrosis factor stimulates transcription of HIV-1 in human T lymphocytes, independently and synergistically with mitogens. 257 6

Details of the molecular interactions between human immunodeficiency virus (HIV-1) and its host cell during the infection process are not entirely clear. Building on recent reports by Lehr and Zimmer (1986, DMW 111, 1001-1002) that the membrane-reactive, anti-epileptic drug diphenylhydantoin (dilantin or phenytoin) (PHT) inhibited binding of HIV to lymphocytes, we hypothesized that understanding the relevant effects of this drug on cells may shed light on aspects of HIV-1 infection. We found that PHT inhibited, in a dose-dependent manner, de novo infection of various T-cell lines as well as a monocytic cell line. Moderate inhibition of HIV-1 infection was observed with drug concentrations that are therapeutic in vivo for epilepsy (approximately 20 micrograms/ml), and no concentrations used induced deleterious effects on cell growth or viability. Surprisingly, treatment of chronically infected H9 cells reduced HIV p24 expression within 1-6 weeks according to dose. This apparent induction into latency was not inhibited by cotreatment of the chronically infected cells with 5-azacytidine, which indicated that PHT was not inducing latency by induction of methylation of the viral DNA. Flow cytometric analysis demonstrated that PHT did not significantly reduce cell-surface expression of CD4. The possibility remained that the drug inhibited HIV infection due to its known effects on calcium-dependent cellular processes. Subsequent measurements of intracellular calcium demonstrated that an increase of [Ca2+]i occurred at least 24 hr postinfection, prior to synthesis of detectable viral structural protein p24, and that this virus-induced increase in [Ca2+]i was not due to binding of HIV to the cell. This HIV-induced rise in [Ca2+]i was significantly inhibited by PHT. PHT demonstrated variable inhibitory effects on infection of normal PHA-stimulated PBLs cultured in vitro, but it was synergistic to low-dose AZT (0.01 microgram/ml) in inhibiting infection of cell lines. Because of the known inhibitory effects of PHT on calcium-dependent biochemical processes in the cell, inhibition of HIV-1 infection by PHT suggests that calcium may play a role in HIV infection and maintenance. The drug may also be a candidate therapy for individuals infected with HIV.
...
PMID:Inhibition of human immunodeficiency virus (HIV-1) infection by diphenylhydantoin (dilantin) implicates role of cellular calcium in virus life cycle. 257 18

<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>