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)

In THP-1 monocytoid cells infected with HIV, viral expression can be regulated in several ways: (a) latency (no viral expression); (b) restricted expression (chronic low-level viral expression with little or no detectable virus released); and (c) continuous production. In cells with restricted HIV expression, nuclear factor(s) were found that blocked tat-associated DNA binding complex formation, suggesting that initiation of transcription was negatively regulated. Also, viral particles were seen budding into and accumulating within intracytoplasmic vacuoles with little virus released, suggesting multiple levels of regulation. These cells with restricted expression had no detectable viral antigens on the cell surface and were not lysed by IL-2-activated large granular lymphocytes. However, they could cause viral-mediated T cell cytolysis in cell-cell assays, suggesting viral transmission through cell contact. In addition, cells with latent HIV were identified and could still produce infectious virus after 5-azacytidine exposure 10 mo later. LPS and other treatments could increase viral production in cells with restricted but not latent expression, suggesting they occur by distinct mechanisms. These infected cells provide a reservoir for viral transmission to uninfected T cells that itself is not detected by immune surveillance mechanisms.
 ...
PMID:Negative regulation of human immune deficiency virus replication in monocytes. Distinctions between restricted and latent expression in THP-1 cells. 233 35

In order to assess the role of alveolar macrophages and their products in the control of Pneumocystis carinii pneumonia (PCP) and other infections in AIDS, bronchoalveolar lavage cells and peripheral blood mononuclear cells from HIV-positive AIDS/ARC patients (with and without PCP) and HIV-negative patients were counted and cultured in vitro; spontaneous and LPS-induced tumour necrosis factor-alpha (TNF-alpha) production was measured. Markedly increased spontaneous TNF-alpha production by alveolar macrophages and, to a lesser extent, peripheral blood monocytes was found in HIV-positive patients with active PCP but not in patients without the infection. Higher TNF production was associated with lower counts of Pneumocystis in the bronchoalveolar lavage fluid. These results suggest that TNF-alpha production by macrophages may play an important role in the control of Pn. carinii infection in AIDS.
 ...
PMID:Alveolar macrophages in AIDS patients: increased spontaneous tumour necrosis factor-alpha production in Pneumocystis carinii pneumonia. 235 41

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.
 ...
PMID:Monokine regulation of human immunodeficiency virus-1 expression in a chronically infected human T cell clone. 246 7

To determine the effects of immunomodulatory agents upon HIV replication in macrophages, cultured monocyte-derived macrophages were treated with various substances and then infected with a macrophage-tropic strain of HIV-1. Pretreatment with rIFN-alpha, IFN-beta, and IFN-gamma, or bacterial LPS prevented viral replication in macrophages. In treated cultures, little or no infectious HIV or p24 core antigen was released into the supernatant, no virions were seen by electron microscopy, no viral RNA or DNA was detectable in the cell lysates, and no cytopathology (as determined by multinucleated giant cell formation) occurred. In contrast, pretreatment with a wide dose range of recombinant IL-1 beta, IL-2, IL-4, IL-6, M-CSF, TNF, or lymphotoxin failed to protect macrophages from productive infection by HIV. A consistent effect of granulocyte/macrophage-CSF on HIV replication in macrophages was not observed. In dose response studies, pretreatment with approximately 100 U/ml of IFN-alpha, approximately 10 U/ml of IFN-beta, or approximately 100 U/ml of IFN-gamma was sufficient to prevent virion release maximally and to prevent cytopathology completely. In kinetic studies, IFN-alpha, IFN-gamma, or LPS were added to the macrophage cultures either before or after infection with HIV. Even when added 3 d after infection with a multiplicity of 1 50% tissue-culture infectious dose per cell, all three treatments markedly reduced virion release, suggesting that these agents act at a point in the viral life cycle beyond the early events of virus binding, penetration, and uncoating. These data indicate that HIV replication in previously uninfected macrophages may be regulated by an inducible host cell mechanism. These findings may explain the restricted replication of HIV in macrophages in vivo and suggest an antiviral role for interferons in the therapy of HIV infection.
 ...
PMID:Interferons and bacterial lipopolysaccharide protect macrophages from productive infection by human immunodeficiency virus in vitro. 246 37

The production of tumor necrosis factor alpha (TNF alpha) and IL-1 beta by the monocytic cell line THP-1, productively infected with HIV-1, was investigated using specific RIA and Northern blot analysis. HIV-infected cells, like uninfected cells, did not constitutively produce any detectable amounts of protein or mRNA for TNF alpha or IL-1 beta. After stimulation with LPS or a combination of LPS plus IFN-gamma, TNF alpha and IL-1 beta were detected in tissue culture supernatants and cell lysates and transcripts for both cytokines were seen on Northern blots. No significant difference in production of these two cytokines was observed between uninfected and chronically infected cells. Acutely HIV-infected cells, however, showed phenotypic changes compatible with maturation and an increase in TNF alpha and IL-1 beta mRNA production, and released significantly higher levels of TNF alpha and IL-1 beta compared with chronically infected or uninfected cells. Furthermore, LPS stimulation of HIV-infected cells increased virus production. These results suggest that HIV-infected monocytic cells may produce increased amounts of TNF alpha and IL-1 beta in response to stimuli that could be present in vivo.
 ...
PMID:Production of tumor necrosis factor alpha and interleukin 1 beta by monocytic cells infected with human immunodeficiency virus. 247 73

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.
 ...
PMID:Viral antigen stimulation of the production of human monokines capable of regulating HIV1 expression. 254 45

Monocytes and tissue macrophages play important roles in host defense against virus infections and, in the case of human cytomegalovirus (HCMV) and HIV, may also be the reservoir for latent disease. Because these cells can also rapidly respond to most infections by secretion of inflammatory mediators, we were interested in determining if HCMV infection could have a direct activating effect on macrophage cytokine production. To do this, we primarily investigated the influence of HCMV infection on IL-1 beta-mRNA expression in peripheral blood monocytes and the promyelocytic cell line, ML-3 as well as the inflammatory response genes TNF-alpha, MAD-9, MAD-6, and MAD-2 in the promyelocytic ML-3 cell line. Exposure of ML-3 cells to the virus prior to induction of differentiation had little influence on mediator gene expression. However, induction of the macrophage phenotype by pretreatment of ML-3 cells with the phorbol ester, PMA, followed by HCMV challenge, resulted in a greatly extended period of expression of IL-1 beta, TNF-alpha, MAD-9, and CSF-1 but not MAD-6 and MAD-2. Constitutively expressed genes such as lysozyme and actin were not similarly modulated. Both RNA dot-blot and in situ hybridization studies demonstrated that infection of human peripheral blood monocytes with HCMV leads to sustained expression of IL-1 beta mRNA for up to 96 h, which contrasted markedly with mock-infected or LPS-stimulated monocytes. Flow cytometric analysis of the intracellular levels of IL-1 beta protein in ML-3 cells indicated that not only was there more protein produced in infected cells, but that the majority of the cells had responded. Enhanced levels of the intracellular form of IL-1 beta in monocytes was confirmed by Western blot analysis. Cotransfection experiments were performed using IL-1 beta-CAT chimeric plasmids together with plasmids encoding HCMV-immediate-early gene region products. Transactivation of the IL-1 beta gene by region 2 of the immediate-early gene was observed in ML-3 cells that had been induced to differentiate prior to transfection. No stimulation of IL-1 beta promoter activity was observed in ML-3 cells that were undifferentiated prior to transfection. In summary, HCMV infection, although not leading to productive infection, nonetheless may contribute to the pathology of the infection through enhancement of monocyte inflammatory mediator gene expression with subsequent stimulation of protein synthesis.
 ...
PMID:Cytomegalovirus infection stimulates expression of monocyte-associated mediator genes. 255 12

Circulating PBMC of healthy subjects possess an in vitro natural antibacterial (NA) against enteropathogenic bacteria, including Salmonella species. The effector cell of NA activity is a CD: 4+, 8-, Leu-8/TQ-1+ T lymphocyte acting against bacteria via cytophylic IgA in a mechanism similar to antibody-dependent cellular activity. Because AIDS is a profound immunodeficiency caused by HIV involving primarily CD4 lymphocytes and in particular the Leu-8/TQ-1 subset, it was of interest to assess NA activity of HIV+ subjects at various stages of the disease. Results indicate that NA activity against Salmonella typhi and Salmonella paratyphi C is significantly decreased in AIDS as well as in lymphadenopathy syndrome patients. Furthermore, sera containing IgA against salmonellae were not able to arm PBMC from HIV+ patients. The humoral response against S. typhi-LPS was also greatly decreased after HIV infection, in contrast to the known hypergammaglobulinemia seen in these subjects. Defective NA activity might contribute to the increased incidence of salmonellosis observed in AIDS.
 ...
PMID:Impairment of in vitro natural antibacterial activity in HIV-infected patients. 326 64

Kaposi's sarcoma (KS) is a neoplasm with multifocal vascular lesions that is often seen in homosexual HIV-infected individuals. Infiltrates of leukocytes are characteristic components of KS lesions, and the products of leukocytes have been shown to enhance the proliferation of KS cells in vitro and most likely are crucial for the development of KS lesions in vivo. It is therefore likely that the expression of cellular adhesion molecules (CAM) is a critical determinant in the pathogenesis of KS by dictating the numbers and types of leukocytes that accumulate in areas predisposed to KS. We report that in the absence of inducers, KS cells in culture expressed low levels of ICAM-1 and undetectable VCAM-1 and E-selectin. ICAM-1, VCAM-1, and E-selectin were all induced by dsRNA (poly (I:C)), IL-1 beta, TNF-alpha, and LPS in KS cells. All of these agents increased NF-kappa B binding activity in nuclear extracts from KS cells. Neither human dermal fibroblasts nor human aortic smooth muscle cells had detectable VCAM-1 protein expression in response to conditions that led to high levels of VCAM-1 expression in KS cells. Although E-selectin expression was induced in KS cells, the peak cell surface protein levels were less than 25% the levels achieved on HUVEC or human dermal microvascular endothelial cells (HMEC). These low levels resembled the levels that were induced in HMEC immortalized with SV 40 large T Ag. These data indicate that multiple proinflammatory agents can induce NF-kappa B binding activity and can enhance ICAM-1, VCAM-1, and E-selectin expression in KS cells. The increased CAM expression enhances leukocyte binding to KS cells. Thus, the induction of CAM expression could be an early event in the development of KS by recruiting leukocytes into KS lesions, thereby providing factors that could potentiate the development of KS.
 ...
PMID:Regulation of adhesion molecule expression in Kaposi's sarcoma cells. 750 14

Serum levels of soluble CD14 were elevated in HIV-infected asymptomatic patients or those with lymphadenopathy (CDC II/III) 2.9 +/- 0.8 mg/l compared with normal controls with 2.2 +/- 0.47 mg/l, P < 0.001. A further rise was seen in patients with ARC (CDC IVA) 3.8 +/- 1.1 mg/l, P < 0.01 and patients with AIDS (CDC IVB-D) 5.7 +/- 2.5 mg/l, P < 0.01. Although absolute numbers of CD14+ cells decrease in the AIDS group, the percentage of CD14+ monocytes did not change. In contrast, levels of soluble T cell antigens sCD4 and sCD8, which are higher in HIV-infected patients compared with normal subjects, showed no increase with disease progression. Serum levels of sCD14 were correlated positively with beta 2-microglobulin levels (rs = 0.63, P < 0.0001). Whereas the percentage of CD14+ monocytes did not change, an increase in monocytic CD14 expression in HIV-infected patients was observed (P < 0.01). The percentage of a monocyte subset expressing both CD14 and CD16 increased from 6% in normal healthy persons to 13% in HIV-infected patients (P < 0.001), and did not vary between the HIV patient groups. Incubation of cultured peripheral blood monocytes with azidothymidine had no effect on either normal or LPS-induced or IL-4-inhibited sCD14 release in vitro. Therefore, an effect of AZT on sCD14 serum values in vivo is considered to be unlikely. Our data further provide evidence that monocytes/macrophages are engaged in HIV infection.
 ...
PMID:Increased soluble CD14 serum levels and altered CD14 expression of peripheral blood monocytes in HIV-infected patients. 752 38


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