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

We studied the effect of human immunodeficiency virus (HIV) infection on the surface-marker expression of the human promonocytic cell line U937. U937 cells persistently produced HIV as detected by reverse transcriptase activity in culture supernatant. Expression of HLA class II antigens on U937/HIV cells was decreased 2- to 10-fold, depending on the Mab used. Class II expression of U937/HIV cells increased approximately two-fold by treatment with r-interferon-gamma. Whereas noninfected U937 cells expressed moderate amounts of lymphocyte function-associated antigen-1 (LFA-1) (CD11a) and minimal amounts of the C3bi receptor (CD11b) and p150/95 (CD11c), U937/HIV cells expressed moderate amounts of C3bi receptor and p150/95 and showed elevated expression of LFA-1 alpha (CD11a) and -beta (CD18) chains. Expression of these adhesion molecules resulted in strongly enhanced phorbolester-induced aggregation of U937/HIV cells compared with the noninfected U937 cells. In addition, almost all U937/HIV cells, but not noninfected U937 cells, intensely stained for cytoplasmic nonspecific esterase activity. The effects of HIV infection on U937 cells strikingly resemble the effects of differentiation-inducing agents, such as PMA and DMSO, on the U937 phenotype. Our finding suggests that HIV infection, apart from down regulating class II expression, induces differentiation of U937 cells.
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PMID:Human immunodeficiency virus infection down-regulates HLA class II expression and induces differentiation in promonocytic U937 cells. 310 23

The molecular mechanism(s) by which human immunodeficiency virus (HIV-1) injures a T-cell line was studied. A pathological role for viral env proteins, which are inserted into the plasma membrane, has been previously demonstrated for HIV as well as other retroviruses which are cytopathic. We therefore initiated studies examining whether perturbations of the cell membrane or membrane-associated biochemical events may be occurring in cells acutely infected with HIV and whether such perturbations, if present, may be responsible for cytopathology. A human T-cell line (ERIC), which is sensitive to the cytopathic effects of HIVs, was infected with HTLV-IIIB and its membrane permeability to cations and its lipid metabolism were studied coincident with the peak expression of viral p24 and with the first sign of cytopathology (slowing of cell division) 72 to 96 hr after infection. It was found that the rate of influx of Ca2+ into the cell increased over that of uninfected cells and that phospholipid synthesis, primarily phosphatidylcholine, became depressed. Diacylglycerol, which serves both as an intermediate for synthesis of phospholipids and as a second-messenger for lymphocyte activation, was also greatly reduced. However, triglyceride synthesis was enhanced, indicating that not all lipid metabolic pathways were being shut down. This decreased membrane-synthetic ability and reduced second-messenger for cell division are likely to be important causes of HIV-1 cytopathology in ERIC cells. This hypothesis was supported by our finding that HIV cytopathology of ERIC cells could be partially prevented by treatment with compounds (diacylglyceride or PMA and transiently by oleic acid) which either replenish diacylglycerol in the infected cell and/or activate protein kinase C or phosphocholine cytidyltransferase, the latter being the rate-limiting step in synthesis of the major structural phospholipid in most cells.
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PMID:Human immunodeficiency virus (HIV-1) cytotoxicity: perturbation of the cell membrane and depression of phospholipid synthesis. 312

The immunoreactivity of paraffin embedded bone marrow biopsies (BMB) was studied following a one step 20-hour-fixation-decalcification in Lowy formalin mercuric chlorid acid solution which permits excellent histological stainings. Antibodies reactive with myeloid, megakaryocytic, erythroid cells, T and B lymphocytes, mastocytes and metastatic cells were compared. Nearly all antibodies working on paraffin sections were demonstrated on Lowy FMA fixed BMB. Special care was taken to define an optimal working dilution. Trypsinization was not necessary. A slide microwave pre-treatment appeared essential before testing CD20 L26, CD8, CD3, CD34, MB1 Kappa and Lambda antibodies. It was suitable for UCHL1, LN2, CD30 antibodies. The same fixative allowed an m RNA Kappa or Lambda in myeloma and EBER 1 EBV RNAs in HIV lymphoma visualization by in situ hybridization. The safety handling of the toxic mercuric chloride component is discussed.
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PMID:Bone marrow one step fixation-decalcification in Lowy FMA solution: an immunohistological and in situ hybridization study. 754 Jul 53

Sixteen biphenyl derivatives were synthesized and evaluated for their inhibitory activity against HIV-1 replication in acutely infected H9 cells. 3-Bromo- (4) and 3,3'-dibromo-4,4'-dimethoxy-5,6,5',6'-bis(methylenedioxy)-2,2'- bis(methoxycarbonyl)biphenyl (5) demonstrated potent anti-HIV activity with EC50 values of 0.52 and 0.23 micrograms/mL and therapeutic index values of > 190 and > 480, respectively. A comparison of the anti-HIV activity of these biphenyl derivatives suggested that the types of substituents on the phenolic hydroxy groups rather than the number of bromine(s) on the aromatic rings are important to the enhanced anti-HIV activity. Compounds 4 and 5 also showed potent inhibitory activity against HIV-1 reverse transcriptase in a template-primer dependent manner. The site of inhibition of HIV could be related to inhibition of this enzyme. Compounds 4 and 5 did not induce virus expression from the chronic HIV-1-infected cell lines ACH-2 and U1. Furthermore, these two agents did not inhibit an increase in virus production from the chronic HIV-1-infected cell lines when the phorbol ester PMA was present.
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PMID:Anti-AIDS (acquired immune deficiency syndrome) agents. 17. New brominated hexahydroxybiphenyl derivatives as potent anti-HIV agents. 754 78

TNF-alpha enhances HIV-1 replication in acutely and chronically infected cells and likely contributes to the wasting associated with the acquired immunodeficiency syndrome. Agents that inhibit TNF-alpha activity should theoretically delay the progression of disease, and several are currently in clinical trials. We hypothesized that IL-10, a cytokine that suppresses the gene expression and synthesis of TNF-alpha in monocytic cells, might inhibit HIV-1 replication. As expected, IL-10 suppressed PMA-induced TNF-alpha production in U1 cells; however, when U1 cells were cultured in the presence of PMA and increasing doses of IL-10, a dose-dependent increase in HIV-1 expression was observed. IL-10 also enhanced IL-1 beta-, TNF-alpha-, and GM-CSF-induced HIV-1 expression in U1 cells, and this occurred, at least in part, at the level of transcription. We next stimulated cells under conditions of TNF-alpha blockade. When PMA-induced TNF-alpha activity and HIV-1 replication were blocked by the presence of soluble TNF receptors, IL-10 independently enhanced HIV-1 replication. In contrast, other agents that are capable of blocking TNF-alpha synthesis or TNF-alpha activity either had no effect (IL-13 and IL-4) or inhibited HIV-1 expression (soluble TNF receptors and pentoxifylline) in U1 cells. These data suggest that IL-10, while inhibiting TNF-alpha synthesis, has an independent mechanism of action that enhances HIV-1 replication. Therefore, IL-10 may have undesirable effects in HIV-1-infected patients.
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PMID:Interleukin-10 enhances human immunodeficiency virus type 1 expression in a chronically infected promonocytic cell line (U1) by a tumor necrosis factor alpha-independent mechanism. 755 27

Patterns of cytokine expression were analyzed in polyclonal and antigenic responses in children with perinatal HIV infection. Responses of PBL to PMA and A23187 calcium ionophore studied in patients in different stages of HIV infection revealed reduced levels of IL-2 in HIV-infected children beginning before 6 mo of age, and age-dependent increases in expression of IL-4, IL-10, and IFN-gamma. The levels of IL-4, IL-10, and IFN-gamma expression did not differ significantly between HIV-infected and age-matched uninfected children of HIV-seropositive mothers, except for a small reduction in HIV-infected children in late stages of infection. Responses to PHA, HLA alloantigens, HIV envelope peptides T1 and P18, and tetanus toxoid were studied in PBMC derived from asymptomatic and mildly symptomatic HIV-infected children. IL-2, IFN-gamma, IL-4, and IL-5 expression was detected in PHA-stimulated PBMC from all analyzed patients. HIV-infected children who failed to respond to HLA alloantigens, tetanus toxoid, or the envelope peptides had lower numbers of CD4+ cells and expressed, on PHA stimulation, higher levels of IL-4 and IL-5 and lower levels of IL-2 and IFN-gamma than patients who responded to the antigenic stimulation. Results of these analyses suggest that cytokine expression in HIV-infected children depends on the character of the stimuli as well as the phenotype of PBMC, and indicate possible prevalence of Th2 Ag-specific responses during the progression of HIV-induced immunodeficiency.
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PMID:Cytokine patterns during progression to AIDS in children with perinatal HIV infection. 756 Nov 17

Although human eosinophils express low concentrations of CD4, the capacity of mature, non-replicating eosinophils to be infected with human immunodeficiency virus-1 (HIV-1) has not been established. Using peripheral blood eosinophils isolated free of contaminating lymphocytes and mononuclear leukocytes, we evaluated eosinophil infection with HIV-1. Eosinophils could be infected with strains of HIV-1 as evidenced by HIV-induced cytolytic effects, progressive release of p24 antigen in cultures of infected eosinophils, recovery of HIV from infected eosinophils by co-cultivation, and detection of HIV-1 gag viral DNA from infected eosinophils by polymerase chain reaction (PCR) amplification. Greater p24 antigen release from infected eosinophils was elicited by the phorbol ester, PMA; and eosinophil killing by HIV-1 was enhanced by the cytokine GM-CSF. By light and electron microscopy, HIV-infected eosinophils demonstrated apoptosis and necrosis. Apoptotic subdiploid nuclear staining was detected by flow cytometric analyses of propidium iodide-stained nuclei from HIV-infected eosinophils, and DNA isolated from HIV-infected eosinophils showed both nucleosomal fragmentation and diffuse degradation. Thus, mature eosinophils, non-replicating terminally differentiated leukocytes, can be infected with HIV-1. HIV-1 expression in eosinophils is promoted by increased granulocyte-macrophage colony-stimulating factor (GM-CSF) and can cause eosinophils to undergo death due to apoptosis and necrosis.
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PMID:Infection, apoptosis, and killing of mature human eosinophils by human immunodeficiency virus-1. 757 98

In HIV-1-infected asymptomatic carriers, the vast majority of infected cells in PBMCs are believed to be latently or nonproductively infected. We have isolated a subclone (MOLT-20-2) from an infected T cell line that expressed HIV-1 Ags at a very low level. However, viral Ag expression was markedly up-regulated by stimulation with either TNF-alpha, A23187, or PMA, indicating that the subclone might provide a suitable model of HIV-1 latency. Our previous studies have shown that the carboxyl-terminal region of the extracellular form of HIV-1 Nef played an important role in the interaction of infected cells with uninfected T cells, and could induce the cytostatic state. This suggested that Nef might contribute to intracellular signal transduction through an interaction with latently infected cells. We show in this study that stimulation of MOLT-20-2 with soluble Nef leads to HIV-1 activation from latency in a dose-dependent manner. Moreover, using a total of 14 overlapping Nef-related synthetic peptides, stimulatory activity was mapped to a discrete peptide (amino acid residues 132-147) that had the potential to activate latent HIV-1. This novel Nef function was confirmed by activation of virus production from the PBMCs of asymptomatic carriers. In addition, Nef-dependent HIV-1 activation from latency was also observed in another independently derived, latently infected cell line, U1, though not in cell line ACH-2. These results extend the significance of the Nef activity in vivo to the regulation of productive HIV-1 infection from latency, and define the regions of the protein involved.
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PMID:Extracellular Nef protein regulates productive HIV-1 infection from latency. 759 42

The HIV viral burden and RNA expression in a selected group of infected, clinically non-progressor patients were investigated. Five fast-progressor patients and 10 AIDS cases were included as controls. The HIV viral load was investigated by semiquantitative polymerase chain reaction (PCR) in adherent macrophages and in genomic and extragenomic fractions of lymphocytes. HIV DNA was not found in macrophages in the non-progressor subjects, was weakly positive in 2 of 5 fast-progressors and strongly positive in most of the AIDS patients. The number of HIV proviruses found in lymphocytes of the non-progressor subjects varied from 5 to 160 copies/microgram DNA, values ten times lower than those recorded in fast-progressors and AIDS patients. The extragenomic HIV DNA (2 LTR forms) was absent or barely detectable in the lymphocytes from non-progressors and abundant in the other groups. HIV RNA was not found in the lymphocytes of all non-progressors. This may indicate that a latent state of HIV provirus exists in the lymphocytes of these subjects. To investigate this point, cultivation and stimulation with PHA (phytohemoagglutinin) and PMA (phorbol 12-myristate 13-acetate) of lymphocytes from these subjects were attempted but after 6 days HIV RNA (RT-PCR for gag region) was still absent or barely detectable in these patients. There are no other reports of the absence of HIV provirus induction in lymphocytes from infected individuals. If confirmed in a larger number of patients, such non-inducibility might serve as a predictor marker of progression of the disease.
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PMID:Peripheral lymphocytes of clinically non-progressor patients harbor inactive and uninducible HIV proviruses. 763 97

Cytokine responses are dramatically affected when HIV-1 infected cells are activated with certain antigenic stimuli. We report the effects of HIV-1 tat gene in cytokine modulation, using HIV-1 tat transfected T (Jurkat) and B (Raji) cell lines. Studying the effect of tat and/or PMA + PHA on mRNA expression of 14 cytokines (IL-1 alpha, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, TNF-alpha, TNF-beta, GM-CSF, TGF-beta, IFN-gamma and MIP-1 alpha) illustrated differential effects. In addition to the varied effects of tat on the steady state levels of cytokine mRNAs, tat induced the secretion of TNF-beta preferentially in both B and T cell lines, either by itself as in Raji B cell line or synergistically upon PMA + PHA stimulation as in Jurkat T cell line.
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PMID:Differential expression of cytokine genes in HIV-1 tat transfected T and B cell lines. 769 26


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