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)

The recombinant plasmid pBHIV-1 carrying the long terminal repeat (LTR) of the human immunodeficiency virus 1 (HIV-1), linked to the reported chloramphenicol acetyl transferase (CAT) gene, was introduced into human and rat fibroblasts. Stable transfectants were obtained which were resistant to genetecin and expressed CAT-activity from the HIV-1 LTR. The response to TNF alpha was studied. It was found that, at the optimum concentration of 100 IU/ml in human and 1000 IU/ml in rat fibroblasts, the expression of CAT was stimulated by 2.1 and 2.5-fold respectively. Our findings suggest that TNF-alpha in physiological concentrations can transcriptionally activate the HIV-1 LTR sequences and this may play an important role in the pathogenesis of HIV infection.
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PMID:Transcriptional activation of the human immunodeficiency virus long terminal repeat sequences by tumor necrosis factor. 129 50

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

Tumor necrosis factor alpha (TNF alpha) levels were determined by enzyme-linked immunosorbent assay (ELISA) and by cell culture bioassay in supernatants of lipopolysaccharide-stimulated feline monocyte cultures and in cat serum samples. There was a good correlation between the results obtained by the two methods. From the fact that TNF alpha was neutralized quantitatively by antibodies to human TNF alpha in feline monocyte supernatants and in feline sera, it was concluded that feline TNF alpha immunologically cross-reacts with human TNF alpha and that the human TNF alpha ELISA can be used to quantitate feline TNF alpha. During the first 6 months after experimental feline immunodeficiency virus (FIV) infection no differences in serum TNF alpha values were observed between infected and non-infected cats. TNF alpha levels increased significantly after primary vaccination with a feline leukemia virus (FeLV) vaccine in FIV infected cats over those in the non-infected controls. During secondary immune response TNF alpha levels rose transiently for a period of a few days in both the FIV positive and the FIV negative cats. After FeLV challenge, TNF alpha levels increased in all animals challenged with virulent FeLV for a period of 3 weeks. This period corresponded to the time necessary to develop persistent FeLV viremia in the control cats. It was concluded from these experiments that in the asymptomatic phase of FIV infection no increased levels of TNF alpha are present, similar to the situation in asymptomatic HIV infected humans. Activation of monocytes/macrophages in FIV infected cats by stimuli such as vaccination or FeLV challenge readily leads to increased levels of TNF alpha.
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PMID:Tumor necrosis factor alpha levels in cats experimentally infected with feline immunodeficiency virus: effects of immunization and feline leukemia virus infection. 133 3

The mechanism for the gradual loss of CD4+ T lymphocytes and the development of the slowly progressive inflammatory/degenerative lesions that accompany human immunodeficiency virus infection are poorly understood. Using the Simian immunodeficiency virus (SIVmac) macaque model of AIDS, we found that persistently infected primary macrophages fuse with primary activated CD4+ lymphocytes and that this interaction results in production of tumour necrosis factor-alpha (TNF alpha) and interleukin 6 (IL-6). An earlier report had shown that SIV-infected macaque macrophages fuse with CEM174 cells (a human CD4+ cell line) and cause their lysis. In the present report, we have shown that TNF-alpha and IL-6 are also produced during the early stages of this interaction. Data from cocultivation of infected macrophages with several CD4+ T cell lines, including CEM174, suggested that the cytokines are produced by the T cells, and that cytokine production is restricted to those cells which not only express CD4, but are also capable of fusing with the infected macrophages. These data suggest that infected macrophages in vivo could fuse with and eliminate activated CD4+ lymphocytes and, during this interaction, release cytokines, which would contribute to the degenerative and inflammatory lesions characteristic of this disease.
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PMID:Tumour necrosis factor and interleukin 6 production during interaction between activated CD4+ lymphocytes and simian immunodeficiency virus-infected macrophages. 135 Mar 3

The derivation of ethyl-methanesulfonate (EMS) mutagenized subclones from the CEM T-cell line has been described. These clones expressed CD4 and bound soluble gp120, however, two of the generated clones were markedly reduced in their ability to form syncytia after infection with either gp160-vaccinia vector or cell-free human immunodeficiency virus type 1 (HIV-1). Here, we asked at what stage(s) viral infection is blocked in these cells. Polymerase chain reaction (PCR) analysis revealed that at 6 and 72 h postinfection with HIV-1, cells of the syncytia-deficient clones expressed markedly reduced amounts of viral-specific DNA compared with cells of the parental line or the syncytia-positive clones. Long-term cultures revealed a marked delay in the appearance of reverse transcriptase (RT) activity in the supernatants of these subclones when compared with the parental line and viral replication did not lead to massive cell death. Syncytia formation in HIV-1-infected cultures of the syncytia-deficient subclones was enhanced by tumor necrosis factor alpha (TNF alpha) when added 24 h postinfection. In contrast, pretreatment with TNF alpha for 48 h followed by washing and infection of the cells with HIV-1 augmented syncytia formation of the syncytia-positive subclones, but not of the syncytia-negative subclones. Thus, the EMS-mutagenized subclones may provide a tool to study host cell factors required for the establishment of a productive HIV-1 infection and responsiveness to TNF alpha.
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PMID:Study of viral replication in HIV-1-infected CEM T-cell subclones which are reduced in their ability to form syncytia. 138 Feb 60

Monocyte/macrophage infection by human immunodeficiency virus type 1 (HIV1) was studied for its effects on the production of tumour necrosis factor alpha (TNF alpha) and the expression of the manganese superoxide dismutase (MnSOD) gene. For this purpose, human peripheral blood monocytes were obtained from healthy HIV1-seronegative donors by centrifugal elutriation and infected with either the HIV1/LAV1 strain or with the primary HIV1/DAS isolate. The results showed that (1) HIV1/LAV1-infected macrophages did not produce any biologically detectable TNF alpha during the few hours following lentiviral infection, despite rises in the TNF alpha mRNA level; (2) MnSOD gene transcription in the macrophages increased, as measured 2 and 4 h after infection; (3) the level of the MnSOD gene expression declined during the late phases of lentiviral infection, but TNF alpha synthesis and gene expression rose; and (4) bispecific antibody comprised of anti-Fc gamma RI (anti-CD64) and anti-gp41 monoclonal antibodies inhibited the in vitro infection of monocyte-derived macrophages by HIV1/DAS.
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PMID:Functional consequences of monocyte/macrophage infection by HIV1. 153 48

The ability of the human immunodeficiency virus (HIV) to replicate in CD+ T lymphocytes and mononuclear phagocytes(MP) is strongly influenced by immunoregulatory cytokines. In the T cell system, interleukin-2 (IL-2) provides a mitogenic signal leading to both cell proliferation and virus replication. Among other HIV-inductive cytokines, only tumor necrosis factor-alpha or -beta (TNF-alpha/-beta) have been shown thus far to trigger virus expression both in T cells and MP. The mechanism of action of TNF involves the activation of the cellular transcription factor NF-kB which binds to specific consensus sequences present in the enhancer region of the HIV proviral LTR. In addition, several other cytokines (including colony stimulating factors, IL-1, IL-3, and IL-6) have demonstrated upregulatory effects on HIV production in MP, whereas nonimmune interferons (INF-alpha/-beta) have been shown to suppress HIV replication in T cells and MP by acting at different phases in the virus life cycle. Finally, cytokines such as TGF-beta, IFN-gamma, and IL-4 have demonstrated either upregulatory or suppressive effects on virus expression depending on the experimental conditions. This scenario indicates that HIV expression is under the control of a complex network of immunoregulatory cytokines, in addition to its own endogenous regulatory proteins, suggesting that new pharmacologic strategies may be aimed at either mimicking or interrupting cytokine-dependent virus expression. In this regard, a number of different physiologic and pharmacologic agents capable of interfering with cytokine-mediated events, including glucocorticoids, anti-oxidants, such as N-Acetyl-L-Cysteine (NAC), and retinoic acid (RA) have already been shown to profoundly affect HIV replication in vitro.
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PMID:The effect of cytokines and pharmacologic agents on chronic HIV infection. 154 Apr 7

Cytokines such as interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF alpha) are produced by leukocytes and play a role in immune responses. They also function in normal brain physiology as well as in pathological conditions within the central nervous system, where they are produced by brain macrophages (microglia) and brain astrocytes. In this study, we document the ability of human immunodeficiency virus type 1 (HIV-1) to induce TNF alpha and IL-1 in primary rat brain cultures. While productive infection did not occur in these cells, it was not required for cytokine induction. Using monocyte/macrophage-tropic (JRFL) and T-cell-tropic (IIIB) strains of HIV-1, we were able to induce cytokines in both microglia and astrocytes. In addition to whole virus, recombinant envelope proteins also induced these cytokines. The induction of IL-1 and TNF alpha could be blocked by a panel of antibodies recognizing epitopes in the gp120 and gp41 areas of the envelope. Soluble recombinant CD4 did not block TNF alpha and IL-1 production. If TNF alpha and IL-1 can be induced in brain tissue by HIV-1, they may contribute to some of the neurologic disorders associated with AIDS.
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PMID:Induction of interleukin-1 and tumor necrosis factor alpha in brain cultures by human immunodeficiency virus type 1. 154 58

We used a sensitive enzyme-linked immunosorbent assay technique to measure tumor necrosis factor alpha (TNF alpha) levels in serum and cerebrospinal fluid (CSF) samples from 30 patients infected with human immunodeficiency virus type 1 and from 10 normal controls. We found detectable levels of TNF alpha in 19 of 30 CSF and in 17 of 30 serum samples. The values of TNF alpha ranged between 20-90 pg/ml. All the patients had overt AIDS. More elevated TNF alpha levels in CSF correlate with focal damage within the central nervous system (p less than 0.01). Our results suggest that an intrathecal production of TNF alpha may occur during active inflammation in course of AIDS.
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PMID:Tumor necrosis factor alpha levels in serum and cerebrospinal fluid of patients with AIDS. 158 76

The induction of human immunodeficiency virus type 1 (HIV-1) gene expression by cytokines was investigated in cells of central nervous system origin. These were human neuroblastoma, glioblastoma, and astrocytoma cell lines, a murine oligodendroglioma and primary murine astrocyte cultures. The cytokines used were tumor necrosis factor alpha (TNF alpha), interleukin-1 beta (IL-1 beta), IL-6, and interferons alpha and gamma (IFN alpha, gamma). Transient transfection of cells with a chloramphenicol acetyltransferase (CAT) reporter gene under the control of the HIV-1 long terminal repeat (LTR) showed significant augmentation following treatment by particular cytokines. TNF alpha was found to augment HIV LTR-directed CAT activity in all cell types. IL-1 beta also activated the HIV LTR reporter gene in glioblastoma, astrocytoma, and astrocyte cells. IL-6 enhanced HIV gene expression in one example only, the primary astrocyte cultures. The interferons generally suppressed expression from the LTR except IFN gamma which produced a twofold rise in the murine glial cells and IFN alpha augmenting expression in one neuroblastoma cell line. No synergy was observed between pairs of activating cytokines tested. The HIV tat gene product was found to be functional in all cells, cotransfection of a tat expression vector transactivating expression from the LTR, with varying degrees of efficiency. In some cell lines the combination of an activating cytokine and tat resulted in an enhancement above that obtained by cotransfection of tat alone. In others, the level of CAT activity did not significantly change. Analysis of nuclear extracts from cytokine-treated cells further implicated the involvement of NFKB in the induction of HIV-1 gene expression.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cytokine augmentation of HIV-1 LTR-driven gene expression in neural cells. 159 55


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