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

The CD25 (IL-2-R alpha) cell surface glycoprotein expressed transiently during T-cell activation is implicated in the high affinity IL-2 receptor. This paper shows that cell-free supernatants from chronically HIV-infected promonocytic cells spontaneously produce a soluble factor which inhibits CD25 expression on PHA-activated human PBMC. We purified the CD25 expression inhibitory activity by a factor 12,350, using XM50 ultrafiltration, Superose 12 molecular sieving chromatography and MonoQ anion-exchange chromatography. Then we associated this activity to one single spot (M(r) 29,000, pI 6.8) on an O'Farrell two-dimensional gel. Our data demonstrate that this protein (M(r) 29,000, pI 6.8) is released from HIV-infected promonocytic cells and suggest that this factor is a new monokine regulating the T-cell activation process.
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PMID:Purification and identification of a CD25 expression inhibitory protein from cell-free supernatants of chronically HIV-infected promonocytic cells. 151 55

Macrophage infiltration is a constant feature of human virus-infected tissues. However, the in situ functional status of these cells remains undetermined. In order to document an activation of macrophages in virus-infected tissues, the expression of IL-1 beta and IL-6 genes was analyzed using in situ hybridization. Several tissues were studied, as well as infections induced by different viruses: lymph nodes infected by HIV-1 (9 cases) or EBV (one case), lungs infected by CMV (5 cases) or adenovirus (1 case), livers infected by HBV, either chronically (2 cases) or acutely (7 cases presenting a fulminant hepatitis). With the exception of fulminant HBV hepatitis, IL-1 beta and IL-6 genes were expressed in all cases. IL-1 beta and IL-6 genes were usually coordinately regulated, as cells containing IL-1 beta or IL-6 mRNA were present in identical amounts and displayed a similar distribution. Analysis of the location and the morphology of monokine gene-expressing cells indicated that both small macrophages and endothelial cells expressed IL-1 beta and IL-6 genes. However, neither tingible body macrophages present in lymph node follicles nor Kupffer cells expressed these genes at a detectable level. Infected cells themselves were also negative for monokine gene expression. These findings indicate that expression of IL-1 beta and IL-6 genes by reactive cells may play a role in viral spreading limitation as well as virus-induced tissue damage.
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PMID:In vivo expression of IL-1 beta and IL-6 genes during viral infections in human. 165 44

Results and conclusions concerning the ability of HIV glycoprotein (gp) 120 to stimulate monokine secretion have been equivocal, based on observations using natural gp120 derived from infected human cells and a Chinese hamster ovary (CHO) cell-derived recombinant fusion protein. Current studies were designed to determine whether differences in recombinant gp120 proteins could result in failure to trigger monokine production. We found that natural gp120 could stimulate monocytes to release TNF-alpha, IL-1 beta, IL-6, and granulocyte-macrophage-CSF, and this effect could be blocked with soluble CD4. Full-length rgp120 either expressed from an adenovirus vector and purified from infected human cells, or derived from CHO cells, could function similarly. In contrast, full-length recombinant envelope protein expressed in a baculovirus system and a CHO cell-derived recombinant fusion protein tested previously, consistently failed to stimulate monokine production. The stimulatory capacity of both natural and full-length CHO cell-derived gp120 was eliminated by heating at 100 degrees C, and could be blocked with excess CHO cell-derived gp120 fusion protein. Inasmuch as the baculovirus-expressed gp120 and the CHO cell-derived recombinant fusion protein can bind to CD4, these results suggest that HIV gp120 binding to CD4 on the monocyte surface may of itself be insufficient for stimulation of monokine secretion. Therefore, primary protein structure, as well as posttranslational protein modifications, may determine this activity.
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PMID:The HIV-1 gp120 envelope protein has the intrinsic capacity to stimulate monokine secretion. 191 97

An investigation was undertaken to determine whether a recombinant gp160 envelope protein, which is currently being evaluated as a vaccine for AIDS, induces or modulates the production of tumour necrosis factor-alpha (TNF-alpha) or interleukin-1 beta (IL-1 beta). Incubation of monocytes from healthy, HIV-seronegative persons with 0.0001-1.0 micrograms of the recombinant vaccine did not result in the secretion of TNF-alpha or IL-1 beta, nor did the recombinant product augment or suppress monokine production by lipopolysaccharide (LPS) stimulated monocytes. The vaccine was also without a stimulatory or modulatory effect upon TNF-alpha or IL-1 beta secretion by monocytes from a patient with the AIDS-related complex (ARC) and from the monocytic THP-1 cell line. The lack of effect of gp160 on monokine production has important implications for its efficacy as a vaccine for AIDS.
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PMID:Effect of a recombinant HIV gp160 vaccine on monokine production. 199 54

A T cell clone (ACH-2) derived from T cells infected with HIV-1 was found to produce HIV-1 in response to stimulation with a monokine-enriched supernatant prepared by culturing human monocyte/macrophages with bacterial LPS (LPS-MO SN). Monokine induction of ACH-2 cells resulted in augmented virus production reflected by an increase in reverse transcriptase activity and in the synthesis of all major viral proteins. Examination of the cells by indirect immunofluorescence revealed that 10 to 15% of uninduced cells constitutively expressed HIV proteins, whereas 100% showed positive immunofluorescence in response to LPS-MO SN. This induction of virus by LPS-MO SN resulted in approximately a 100-fold increase of infectious virus production over uninduced ACH-2 cells. LPS alone could not induce HIV-1 expression, whereas LPS-MO SN resulted in the greatest virus expression. Cell separation studies confirmed the source of the inducing factor(s) to be cells bearing the mature monocyte/macrophage marker, Leu M3. Biochemical fractionation of the LPS-MO SN suggested that one or more factors, having apparent Mr of approximately 45 kDa, were involved in this induction. Absorption of the LPS-MO SN with immunoaffinity gels specific for human TNF-alpha was shown to completely remove the HIV inducing activity for the ACH-2 cell line.
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PMID:Monokine regulation of human immunodeficiency virus-1 expression in a chronically infected human T cell clone. 246 7

We have previously described model systems for cytokine-induced regulation of chronically HIV-infected promonocyte and T cell clones. Using these systems, we have shown that monokines contained in supernatants from LPS-stimulated human monocyte/macrophages (MO) up-regulate HIV expression, reflected by an increase in reverse transcriptase activity, viral RNA levels, and expressed viral proteins. Current studies were designed to determine whether viral Ag can interact with MO and secondarily affect HIV1 expression by stimulating monokine production. We found that certain herpes-group viruses, including CMV and EBV, augment HIV1 expression by inducing monokine production, whereas others, such as HSV1, HSV2, varicella-zoster virus, and human herpes virus 6 were unable to function in this capacity. The HSV1 and HSV2 Ag which failed to stimulate monokine production did not interfere with MO stimulation by CMV Ag, suggesting that failure to induce HIV expression was not attributable to MO suppression. When nonherpes group viruses were tested, we found that human adenovirus, hepatitis B virus, and vaccinia virus all failed to stimulate the production of monokines capable of activating HIV in the chronically infected cell lines. In contrast, HIV1 can augment its own expression by inducing the secretion of monokines which up-regulate HIV expression in the infected cells. The viral Ag-induced MO supernatants capable of up-regulating HIV expression did so in a dose-dependent manner, whereas viral Ag alone produced no significant change. Monokine production mediated by viral Ag was not attributable to contaminating endotoxin. These studies provide a model to determine whether other opportunistic infections may induce the expression of HIV by indirect mechanisms, such as the stimulation of cytokine production.
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PMID:Viral antigen stimulation of the production of human monokines capable of regulating HIV1 expression. 254 45

We measured simultaneously circulating and cell-generated TNF-alpha and IL-1 after lipopolysaccharide (LPS) stimulation of peripheral blood mononuclear cells (PBMC) by radioimmunoassay (RIA) in HIV-infected individuals at different stages of infection, classified according to CDC classification. TNF-alpha production, both in vitro and endogenous in sera, remained at the normal level in group II patients but was significantly increased in most patients in group IV (P less than 0.05). Most patients of group II and IV displayed normal level of IL-1 in their sera, whereas the level of this monokine generated in vitro was significantly reduced in both groups (P less than 0.05). The cytotoxic effect of factor(s) secreted by PBMC from HIV-infected individuals was evaluated towards a fibroblast cell line L929. The higher titre of cytotoxicity was directly related to a higher production of TNF-alpha by the cells from group IV patients and the effect could be removed by pre-absorption with anti-TNF-alpha monoclonal antibody.
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PMID:Production of tumour necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1) in patients with AIDS. Enhanced level of TNF-alpha is related to a higher cytotoxic activity. 261 49

HIV-infected patients are at markedly increased risk for neurological dysfunction, which may occur at any level of the neuraxis (see Table 1). The most common syndromes--AIDS dementia complex, vacuolar myelopathy, and possibly distal symmetric peripheral neuropathy--appear to be related to HIV infection within the nervous system, rather than due to the immunoincompetence caused by HIV. However, the mechanism(s) by which HIV causes these syndromes, e.g., infecting neurons or oligodendroglia directly, interfering with neurotrophic factors, effecting toxic monokine production, etc., is unknown. Early, albeit incomplete, success with azidothymidine is encouraging. Less commonly, neurological syndromes may be secondary to the immunoincompetence produced by HIV. Many different etiologies--most of which are treatable--have been encountered, but a few of these (cerebral toxoplasmosis, cryptococcal meningitis, primary CNS lymphoma, and progressive multifocal leukoencephalopathy) are responsible for most of the opportunistic complications. Marked differences in symptoms and signs between AIDS patients and immunologically normal patients may complicate recognition of some of these diseases (e.g., herpes simplex encephalitis). Finally, some HIV-associated syndromes, e.g., inflammatory demyelinating polyradiculoneuropathy and retinal microvasculopathy, are of unknown etiology.
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PMID:The neurology of human immunodeficiency virus infection. 285 54

Elevated levels of circulating monokines (IL-6, IL-1, and TNF alpha) have been seen in HIV-1 infection, and the overproduction of these cytokines could contribute to AIDS pathogenesis in various ways. In previous work, we had seen that exposure of human monocytes to HIV-1, including inactivated, noninfectious HIV, led to rapid IL-6 gene expression and secretion. To investigate cytokine production in response to components of HIV by monocytes/macrophages, production of IL-6 and IL-10 were examined in a human monocytic cell line, THP-1, stimulated by HIV proteins. IL-6 production was induced in THP-1 cells by a detergent lysate of HIV, particularly fractions at molecular weight of 25-50 kDa. Recombinant HIV envelope glycoprotein 41 (gp41), but not gp120 or p24, also was seen to induce significant IL-6 production by THP-1 cells. These results suggest that gp41, transmembrane protein, is the primary HIV-encoded protein involved in inducing IL-6 production. IL-10 was also produced with delayed kinetics, following IL-6 production in THP-1 cells stimulated by gp41. To investigate a possible regulatory role for IL-10 in HIV-induced monokine production, recombinant IL-10 was added to gp41-exposed THP-1 cells. IL-10 inhibited gp41-induced IL-6 production and reduced the expression of IL-6 mRNA. When anti-human IL-10 neutralizing antibody was added to THP-1 cells, IL-6 production was enhanced. These results suggest that the IL-6 production may be downregulated by endogenously produced IL-10 and that IL-10 may downregulate cytokine production by HIV-activated monocytes via an autoregulatory mechanism.
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PMID:Induction of IL-6 and IL-10 production by recombinant HIV-1 envelope glycoprotein 41 (gp41) in the THP-1 human monocytic cell line. 755 88

The effects of cysteamine (2-aminoethanethiol, MEA) and its disulfide, cystamine, on the human immunodeficiency virus (HIV-1) expression in chronically infected promonocytic cells (U1), T cell line (ACH-2), and peripheral blood monocyte-derived macrophages (MDM) were investigated. U1 and ACH-2 cells constitutively express low levels of virus, which is increased by the addition of tumor necrosis factor (TNF-alpha), interleukin 6 (IL-6), granulocyte-macrophage-colony-stimulating factor (GM-CSF), and other inducers. Cystamine, in noncytotoxic doses, suppressed in a concentration-dependent fashion the induction of HIV-1 expression mediated by TNF-alpha, IL-6, GM-CSF, and monokine-enriched monocyte culture supernatants in both U1 and ACH-2 cells as determined by HIV-1 reverse transcriptase (RT) activity. Similarly, HIV-1 expression was substantially reduced in the cystamine-treated primary MDM cultures compared with the untreated control cultures. The addition of cystamine into HIV-1 chronically infected MDM (12 days after infection was established) also suppressed 80-90% of RT activity in comparison to the untreated controls. HIV-1 (Bal) infected MDM cultures (without cystamine treatment) demonstrated giant syncytium formation, whereas cystamine-treated cultures lacked the giant syncytia induced by HIV-1 infection. Cystamine also inhibited LPS-induced TNF production in MDM. In contrast to cystamine, cysteamine showed no significant effects on either the monokine-induced HIV-1 expression in U1 or ACH-2 or acute and chronic HIV-1 infection in MDM.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cystamine inhibits HIV type 1 replication in cells of monocyte/macrophage and T cell lineages. 763 61


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