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

We examined the interaction between HIV-1 Tat protein and the opportunistic pathogen Mycobacterium avium. AIDS-associated strains of M. avium were shown to bind Tat protein quite avidly in an attachment assay. The attachment of M. avium to Tat was shown to occur via the integrin alpha 5 beta 1 present on the mycobacterial cell surface. M. avium strains were shown to bind the viral Tat protein with high affinity in a specific fashion (600 binding sites with a Kd of 1 to 5 nM). M. avium coated with Tat protein were shown to be more infective for human alveolar macrophages than untreated M. avium. Other HIV-1 Ags had no such effects (e.g., p24, p17). Examination of the cytokine profile of infected macrophages showed that M. avium-Tat complexes induced higher levels of TGF beta-1 (TGF beta 1) than M. avium alone or M. avium that had been in contact with other viral proteins. Conditioned media from HIV-1-infected H9 cells released a factor that enhanced M. avium intramacrophage growth, and was partially neutralized by an anti-Tat Ab. Finally, Tat protein (purified or present in conditioned media from infected cells) moderately enhanced the growth of M. avium strains in extracellular media, and exposure of M. avium to Tat protein in the presence of IL-6 enhanced the growth of AIDS-associated strains. These data argue for an interaction between the Tat viral product and the opportunistic pathogen M. avium which may contribute to the exquisite susceptibility of AIDS subjects to this pathogen.
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PMID:Tat protein from HIV-1 binds to Mycobacterium avium via a bacterial integrin. Effects on extracellular and intracellular growth. 805 12

The two fragments of HIV-1 gp120 molecule were synthesized to study their interaction with human monocytes. Previous observations indicated that recombinant gp120 fragment (aa residues 410-511) encompassing CD4 binding region (rp120cd) induced tumour necrosis factor alpha (TNF) production in monocytes, while a similar fragment (rp120) not containing the CD4 binding sequence (aa 446-511) was inactive. This paper shows that rp120cd depressed monocyte ability to present antigen (PPD) to autologous T lymphocytes while rp120 was noninhibitory. The rp120cd interacted with monocytes but not T lymphocytes. Anti-TNF receptor type A antibody (utr-1) prevented the depression of antigen presentation caused by rp120cd, which suggested a role for TNF and its receptor. The depression of antigen presentation was seen only when monocytes were treated with rp120cd before, but not after, pulse with antigen. Parallel changes were observed in PPD-induced IL-6 production. Thus, induction of TNF by gp120 may be associated with impairment of antigen-presenting capacity of monocytes seen in AIDS patients.
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PMID:Modulation of antigen-presenting capacity of human monocytes by HIV-1 GP120 molecule fragments. 807 Aug 47

Because HIV may alter the production of inflammatory factors produced by monocytes, the expression of tumor necrosis factor alpha (TNF-alpha), tissue factor (TF), interleukin (IL)-1 beta, and IL-6 was evaluated in 47 HIV-seropositive persons and seronegative control subjects. RNA was extracted from freshly isolated lipopolysaccharide (LPS)-stimulated or unstimulated monocytes. Cytokine and TF expression was quantitated by dot blot hybridization or a reverse transcription polymerase chain reaction (RT-PCR). A significant depression of TF mRNA was observed in LPS-stimulated monocytes (66% less in AIDS, 20% less in AIDS-related complex (ARC), and 0% less in asymptomatic patients), whereas normal responses were observed for TNF-alpha, IL-1 beta, and IL-6. When constitutive expression was measured in unstimulated monocytes by RT-PCR, a differential pattern was also observed. TNF-alpha and IL-1 beta were positive in 85% of asymptomatic persons, compared with only 27% of ARC and 42% of AIDS patients. Expression of IL-6 was observed in lower proportions, 27-30%, with no significant differences among disease states. All samples were negative for TF. Thus, the regulation of inflammatory molecules is differentially altered in individuals with HIV infection. TF is preferentially down-regulated, compared with TNF-alpha, IL-1 beta, and IL-6, in LPS-stimulated monocytes as patients progress to AIDS. TNF-alpha and IL-1 beta are preferentially up-regulated, compared with IL-6 and TF, in unstimulated monocytes in asymptomatic persons, with a loss of up-regulation as patients progress to AIDS.
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PMID:Dysregulation of cytokine expression in monocytes from HIV-positive individuals. 808 6

B cell dysfunction associated with HIV infection includes polyclonal B cell activation and hypergammaglobulinemia. There is also an elevated frequency of B cell malignancies, especially non-Hodgkin's lymphoma, in HIV infection. It is believed that chronic polyclonal activation of B cells might increase the chances for the occurrence of a genetic accident, resulting in tumorigenesis. Long-term zidovudine use in people with HIV infection has been reported to be associated with a particularly high incidence of B cell lymphoma. This may be due to an increase in life span associated with antiretroviral treatment, placing treated individuals at risk for developing lymphoma for a greater period of time. However, zidovudine could be directly contributing to lymphoma-genesis in HIV-infected individuals, perhaps by enhancing B cell activation, since B cell hyperactivation and elevated levels of IL-6, a B cell stimulatory cytokine, are seen in HIV infection. Also, people treated with zidovudine may inherently be at higher risk for developing lymphoma because of the relatively greater degree of immune impairment seen in those that receive treatment with this drug. To examine if exposure to zidovudine resulted in enhanced B cell activation, we determined whether or not the presence of zidovudine enhanced B cell activation or IL-6 production in vitro or in vivo. Exposure to zidovudine in vitro did not enhance spontaneous immunoglobulin or IL-6 secretion by cells from HIV-infected (or uninfected) subjects and did not enhance B cell activation induced by EBV or affect the ability of T cells to regulate EBV-activated B cells. Neither serum immunoglobulin or IL-6 levels, nor the expression of cell surface activation markers on circulating B cells, were seen to increase following zidovudine treatment. These results indicate that zidovudine does not induce B cell activation in vivo or in vitro, suggesting that zidovudine treatment does not contribute to lymphomagenesis by enhancing B cell hyperstimulation.
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PMID:Effects of zidovudine on B lymphocyte activation. 808 61

The membrane-bound glycoprotein intercellular adhesion molecule 1 (ICAM-1) plays an important role for many cell-contact-dependent immune functions. A soluble, circulating form of ICAM-1 (cICAM-1) has been detected in the serum of healthy persons and increased concentrations in tumor patients have been reported. We measured serum levels of cICAM-1 in HIV-1-infected individuals with a recently developed ELISA. In contrast to HIV-seronegative controls (median value of 294 ng/ml, range of 185-408 ng/ml; n = 22), significantly elevated concentrations were detected in 76 HIV-1-infected persons (median of 487 ng/ml, range of 231-1,524 ng/ml; p < 0.0001). In HIV-1-infected individuals, cICAM-1 values did not correlate with the absolute number of CD4+ T cells or with disease progression according to the Walter Reed staging classification. Concentrations of cICAM-1 correlated with the serum concentrations of IL-6 (p = 0.0015; Spearman's rank correlation analysis) and with urinary neopterin (p = 0.005), but not with the C-reactive protein. Since there is evidence that cICAM-1 can interfere with immunological functions, the high amounts circulating in HIV-1-positive individuals could contribute to the disturbance of the immune system in HIV-1 infection.
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PMID:Elevated concentrations of circulating intercellular adhesion molecule 1 (ICAM-1) in HIV-1 infection. 809 41

Oncostatin M (OM), a 30-kDa glycoprotein, recently was identified as a major growth-promoting factor in the conditioned medium (CM) of the 38-0 cell line, a CD4,+ chronically human T lymphotropic virus type (HTLV)-II-infected, transformed T cell line. CM 38-0 induced the proliferation of spindle cells cultured in vitro from AIDS-associated Kaposi's sarcoma (AIDS-KS) cells. To determine how much of the AIDS-KS cell growth activity present in 38-0 CM was because of the presence of OM, we depleted OM by using specific mAb-affinity chromatography. OM purified from this CM stimulated AIDS-KS cell growth in a concentration-dependent fashion. The effluent, completely depleted of OM, failed to induce growth of AIDS-KS cells. To detect the constitutive release of OM by cells acutely or chronically infected with either HTLV-I, HTLV-II, or HIV-1, we utilized an enzyme-linked immunoassay. Whereas the chronically infected cells released significant levels of OM, the acutely infected cells released little or no OM. The presence of OM in HIV-1-infected T-cell CM correlated completely with AIDS-KS cell growth activity. Infrequently, low level AIDS-KS cell growth activity was seen in the absence of OM. This correlated with relatively high levels of IL-6 in the CM. In a CM-containing OM in the absence of detectable IL-6, a neutralizing antibody to OM completely abrogated KS cell growth activity. The presence of specific oncostatin M receptors on the KS cell lines was confirmed by cross-linking experiments. The results shown here suggest that T cells chronically infected with HIV-1 can secrete OM, which may play a role in the initiation or progression of AIDS-KS lesions, either alone, or in concert with IL-6.
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PMID:Correlation of oncostatin M secretion by human retrovirus-infected cells with potent growth stimulation of cultured spindle cells from AIDS-Kaposi's sarcoma. 809 26

This chapter has summarized studies showing that cells of the immune system and glial cells of the CNS use many of the same cytokines as communication signals. Activated astrocytes and microglia are the principal sources of these cytokines in the CNS, although oligodendrocytes are capable of expressing IL-1 and TGF-beta. There is a complex circuitry of interactions mediated by cytokines, especially in the event of blood-brain barrier damage and lymphoid/mononuclear cell infiltration into the CNS. Infiltrating activated macrophages produce cytokines such as IL-1, TNF-alpha, and IL-6, which would trigger glial cells to produce their own cytokines. The activation of astrocytes and microglia to secrete proinflammatory cytokines such as IL-1, TNF-alpha, IL-6, and GM-CsF may contribute to the propagation of intracerebral immune and inflammatory responses initiated by immune cells, as well as enhancement of HIV-1 expression in the CNS. The cytokine cascades ongoing in the CNS could ultimately be suppressed due to the presence of immunosuppressive cytokines such as TGF-beta. Whether immune and inflammatory responses within the CNS are propagated or suppressed depends on a number of parameters, including (a) the activational status of these cells, (b) cytokine receptor levels on glial and immune cells, (c) the presence of cytokines with both immune-enhancing and immune-suppressing effects (IFN-gamma, IL-1, TNF-alpha, IL-6, TGF-beta, CsFs), (d) the concentration and location of these cytokines in the CNS, and (e) the temporal sequence in which a particular cell is exposed to numerous cytokines (see Fig. 1). The ultimate outcome of immunologic and inflammatory events in the CNS, as well as HIV expression, will be determined, in part, by an interplay of the above parameters.
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PMID:Cytokine circuits in brain. Implications for AIDS dementia complex. 811 22

Research progress in the understanding of HIV and its effects on the human immune system continues at a rapid pace. Such research is yielding new ideas for chemotherapeutic agents, immunologic stimulators and modifiers, and potential vaccines. Clinical trials to test these approaches are under way. Despite the accomplishments, the epidemic progresses unchecked, resulting in continued suffering and death and enormous demands on the health care system of many nations. Clinicians have had to deal with new and difficult opportunistic infections. Yet advances in the treatment and prevention of these illnesses have benefited many AIDS victims. In the United States, the AIDS epidemic is now concentrating in the inner cities, involving injection drug users, minorities, heterosexuals, women and their offspring. In the developing world, AIDS continues to be predominantly a heterosexually transmitted disease, where more than one third of prostitutes in central African cities are infected. The major burden of the AIDS epidemic in the remainder of this and the next century will be in India and Southeast Asia, again predominantly via heterosexual spread. A great deal is now understood concerning the life cycle of HIV. More light has been shed on the interaction of HIV and CD4+ T cells, the cellular and viral factors involved in viral expression vs. latency, the function of the viral regulatory and structural proteins and the role of cytokines in regulation of HIV expression. Our understanding of the precise mechanisms whereby HIV causes a loss of CD4+ T cells remains incomplete. The direct infection and cell killing of CD4+ T cells is important and is supported by recent evidence demonstrating a high viral burden in these cells in the lymphoid tissue of patients. Over the last 1 to 2 years, there has been new evidence for indirect mechanisms of CD4+ T-cell depletion and/or dysfunction including: autoimmune reactions, perturbations of specific V beta T-cell receptor populations, infection of T-cell precursors in bone marrow and thymus, immunosuppression and dysregulation by viral proteins, possible super-antigen effects, and antigen-induced apoptosis or programmed cell death. New information has come forth in our understanding of B-cell abnormalities in HIV pathogenesis, including the putative role of IL-6 in B-cell activation and the identification of EBV in B-cell lymphomas in the CNS of patients with AIDS. It is expected that these and future discoveries concerning immunopathogenesis of HIV infection will help steer the therapeutic effort. Major strides continue to be made in the therapeutic arena for HIV infection and its complications.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Human immunodeficiency virus and acquired immunodeficiency syndrome: an update. 814 Sep 58

Vesnarinone, a synthetic oral cardiotonic agent that has been used for treatment of patients with congestive heart failure, was found to inhibit replication of HIV-1 in a peripheral blood lymphocytes model and in chronically infected macrophages at clinically achieved concentrations. Vesnarinone has no direct inhibitory activity against the reverse transcriptase of HIV-1, syncytium formation in short term assays, or retroviral protease. In addition, vesnarinone inhibits production of TNF-alpha and IL-6 by human peripheral blood mononucleated cells stimulated with LPS. These observations suggest that vesnarinone may be therapeutically useful in patients infected with HIV-1.
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PMID:Vesnarinone inhibits production of HIV-1 in cultured cells. 821 57

The myeloid-monocytic cells ML-1, HL-60, THP-1 and U-937 were chronically infected (for more than 2 years) with the lymphotropic HIV-1 strain HTLV-IIIB. Reinfection experiments revealed that viruses obtained from chronically infected ML-1/HIV-1 and HL-60/HIV-1 cells show a low infectivity if tested with uninfected ML-1 and HL-60 cells in contrast to virus preparations from chronically infected THP-1/HIV-1 and U-937/HIV-1 with their corresponding uninfected cell lines. Analyses of selected cell surface markers showed a differential expression of CD4, CD8, CD11c, CD14, CD15, CD20, HLA-DR and HLA-DQ in non- or chronically infected cells. During chronical infection, the myeloid-monocytic cells lost their reactivity with peroxidase and esterase. In chronically infected cells, the steady-state levels for TNF-alpha mRNA remained unchanged while those for IL-6 decreased. The half-lives of transcripts of both TNF-alpha (t1/2: 70 min) and IL-6 (t1/2: 100 min) were nearly the same in uninfected and chronically infected HL-60 cells.
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PMID:Characterization of cells of the myeloid-monocytic lineage (ML-1, HL-60, THP-1, U-937) chronically infected with the human immunodeficiency virus-1. 821 36

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