Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The p17 matrix protein of the human immunodeficiency virus type 1 (HIV-1) plays a crucial role in AIDS pathogenesis. It orchestrates viral assembly and directs the preintegration complex to the nucleus of infected cells. Recently, the three-dimensional structure of p17 was shown to resemble that of interferon-gamma (IFN-gamma), suggesting that both proteins might share analogous functions. We demonstrate that in monocytes, p17 shares with IFN-gamma the ability to induce 1alpha-hydroxylase activity and to activate fructose 1,6-bisphosphatase gene expression in the presence of 25-hydroxyvitamin D3. However, p17 does not bind to the IFN-gamma cell membrane receptor and fails to increase expression of IFN-gamma-induced proteins, such as tryptophanyl-tRNA synthetase, Fc gammaRI, and HLA DR or B7/BB1 antigens. Altogether, our results raise the possibility that the structural resemblance between p17 and IFN-gamma causes the selective activation of a common pathway resulting in the production of 1,25-dihydroxyvitamin D3. We also found that unlike IFN-gamma, p17 increases the intracellular ATP content. Since transport of the HIV-1 preintegration complex through the nuclear membrane is an ATP-dependent process, our observation suggests that p17 plays a double role in this active transport, not only by acting as a chaperone molecule but also by recruiting the necessary energy for this process.
J Interferon Cytokine Res 1997 Aug
PMID:HIV-1 p17 and IFN-gamma both induce fructose 1,6-bisphosphatase. 928 26

A DNA vaccine constructed with the CMV promoter conjugated to env gp160 and rev genes has been shown to induce an effective Th1-type immune response when inoculated via an intramuscular route. In the present study, we obtained high levels of both humoral and cell-mediated immune activity by intranasal administration of this DNA vaccine. The production of mucosal IgA Ab in feces and vaginal fluid was stimulated significantly by intranasal DNA administration. This route of administration resulted in a significant level of HIV-1-neutralizing Abs in feces and serum. Cytokine assays revealed that intranasal administration of this DNA vaccine induces a Th2-type immune response. Interestingly, cationic liposomes greatly enhanced these activities. Abs against HIV-1 were present for at least 10 mo. Coadministration of the DNA vaccine with IL-12- and granulocyte/macrophage-CSF-expressing plasmids induced high levels of HIV-specific CTLs and an increase in delayed type hypersensitivity when administered by the intranasal route. These results clearly demonstrate that intranasal administration of this DNA vaccine with liposomes, together with IL-12- and/or granulocyte/macrophage-CSF-expressing plasmids, induces a strong level of anti-HIV-1 immune response.
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PMID:Intranasal immunization of a DNA vaccine with IL-12- and granulocyte-macrophage colony-stimulating factor (GM-CSF)-expressing plasmids in liposomes induces strong mucosal and cell-mediated immune responses against HIV-1 antigens. 931 64

Quinolinic acid (QUIN) has been associated with several inflammatory neurologic disorders, including AIDS dementia complex (ADC). Recent studies suggest that activation of macrophages with either HIV-1 or interferon-gamma (IFN-gamma) can lead to QUIN production. However, the importance of other cytokines, especially those related to the macrophage and that are especially important in ADC pathogenesis, remains unclear. We, therefore, sought to determine the role of tumor necrosis factor-alpha (TNF-alpha) and IFN-alpha in the production of QUIN. Primary human macrophages were stimulated with two different concentrations of these cytokines alone, in combination with each other, and with IFN-gamma. QUIN concentrations in the supernatants were then measured by mass spectrometry at 24, 48, and 72 hs. Results at 72 h showed significant increases in QUIN production in the cells stimulated with IFN-gamma (10297 +/- 170 nmol/L) and also in those stimulated with IFN-alpha (3600 +/- 113 nmol/L), whereas TNF-alpha-stimulated macrophages produced low levels of QUIN (1108 +/- 23 nmol/L). Macrophages stimulated with the cytokine combinations TNF-alpha and IFN-gamma, IFN-alpha, and IFN-gamma, and TNF-alpha and IFN-alpha also resulted in increases in QUIN production (11471 +/- 77.6 nmol/L, 16656 +/- 184 nmol/L, and 3369 +/- 120.5 nmol/L, respectively). The increases in QUIN production in all of the cytokine treatments approached or exceeded in vivo concentrations of QUIN that have been shown to be neurotoxic. These data further support a role for QUIN in cytokine-mediated neuronal death in inflammatory disorders of the brain, especially ADC.
J Interferon Cytokine Res 1997 Oct
PMID:Quinolinic acid production by macrophages stimulated with IFN-gamma, TNF-alpha, and IFN-alpha. 935 59

Ameboid microglia express human immunodeficiency virus 1 (HIV-1) more frequently than do ramified microglia. These two microglial subtypes might also differ in the frequency with which they express transforming growth factor-beta1 (TGF-beta1), a cytokine that regulates HIV-1 expression in monocytes. Results described here show that ameboid and ramified microglia express TGF-beta1. In brain tissues from HIV-1-infected individuals as compared with seronegative controls, ameboid rather than ramified microglia more frequently expressed TGF-beta1. Ameboid microglia, isolated and cultured from postmortem adult human brain more frequently expressed TGF-beta1 in presence of interleukin-1(IL-1), a cytokine that is elevated in brains of HIV-1-infected individuals when compared with seronegative controls. The stimulation of TGF-beta1 by IL-1 was dose and time dependent, occurring with ameboid microglia isolated from either frontal cortex or globus pallidus but not midbrain pons. Ameboid microglia are similar to the RCA-1-positive cells that form clusters, called microglial nodules, in the brain of HIV-1-infected individuals. Pathologic conditions, such as disseminated microglial nodules, are associated with HIV-1 encephalitis, direct infection of the brain, and moderate to severe neurologic impairment. TGF-beta1 expression in ameboid microglia may play a role in HIV-1 neuropathogenesis.
J Interferon Cytokine Res 1997 Nov
PMID:Transforming growth factor-beta1 in adult human microglia and its stimulated production by interleukin-1. 940 3

The current study examined the proliferative capacity and cytokine secretion pattern of peripheral blood mononuclear cells (PBMC) from human immunodeficiency virus type 1 (HIV-1)-infected patients in response to the major surface glycoprotein (MSG) of Pneumocystis carinii. PBMC from AIDS patients with <200 CD4 cells/mL had significantly less proliferative responses to MSG than did healthy controls. Cytokine analysis indicated that interferon-gamma secreted in response to MSG was also significantly less. There was no significant difference in interleukin-4 levels following incubation with MSG between any of the groups; however, all the HIV-infected persons had slightly elevated levels. When the CDC class C3 patients who had a previous episode of P. carinii pneumonia were compared with those who had not had a previous episode, there was a significant increase in the proliferative response to MSG and in interleukin-4 secretion. CDC class C3 patients who had a previous episode of P. carinii pneumonia showed a predominately Th2 response to MSG.
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PMID:Proliferative and cytokine responses of human T lymphocytes isolated from human immunodeficiency virus-infected patients to the major surface glycoprotein of Pneumocystis carinii. 941 98

Infection of rhesus monkeys with SIV leads to AIDS-like symptoms. Similar to human AIDS patients, some monkeys develop B cell non-Hodgkin lymphoma (NHL). We determined transcription of cytokine genes regulating the activation of B and T cells, which play a role in intratumoral immune surveillance. Therefore, we compared the transcription of the cytokine genes encoding IL-2, IL-4, IL-6, IL-10, IFN-gamma, TNF-alpha, and TGF-beta1, and the Epstein-Barr virus-encoded BCRF 1 gene, in cells from five monkey and two human tumor specimens. The immune-suppressive IL-10 and TGF-beta1 genes were predominantly transcribed in all tumor specimens analyzed. Cytokine gene transcription patterns appeared to be similar in human and animal tumor cells. The transcription patterns corresponded to their histological classification as diffuse large-cell lymphoma according to the REAL classification and as immunoblastic or centroblastic tumors according to the Kiel classification. The determination of cytokine gene transcription pattern in the NHL may improve our understanding of pathogenesis and immune surveillance in this heterogeneous group of tumors. Our data show that SIV-associated NHLs of rhesus monkeys are comparable to human HIV-1-associated EBV-positive non-Hodgkin lymphoma.
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PMID:Cytokine gene transcription in simian immunodeficiency virus and human immunodeficiency virus-associated non-Hodgkin lymphomas. 943 Feb 51

Cytokine dysregulation is evident in HIV-1 infection and it may play an important role in HIV-1 pathogenesis. Administration of T helper cytokines potentially may restore the functional abnormalities to the HIV-1 immune response. Type 1-like cytokines, IL-2, IL-12, and IL-15, are candidates for immune-based therapy for HIV. Given their potential therapeutic use, we determined the effects of IL-2, IL-12, and IL-15 on HIV-1 replication in both primary blood mononuclear cells (PBMC) and the T-cell line, Kit 225-K6. We demonstrate that both IL-2 and IL-12 induce a similar level of HIV-1 replication (9- and 11-fold, respectively) in mitogen-stimulated PBMC. The effect of IL-2 plateaued by day 6, while that of IL-12 continued to increase HIV-1 expression. IL-15 induced a 2.5-fold increase in HIV-1 expression that remained at the same level through day 6. In Kit 225-K6, an IL-2-dependent T cell line, IL-12 and IL-15 enhanced HIV-1 replication by 5- and 3.5-fold over IL-2-treated cultures, respectively. IL-2-, IL-12-, and IL-15-mediated induction of HIV was independent of direct HIV-1 LTR activation, since none of the cytokines induced LTR activity from transfected reporter gene constructs. The cytokine-mediated induction of HIV-1 expression was also independent of cellular proliferation. In PBMC, the IL-12-mediated effect was partially mediated by endogenous cytokine production of IL-1beta and IL-7, whereas in Kit 225-K6, TNFalpha, INFgamma, IL-1beta, and IL-7 did not contribute significantly to the IL-12-mediated effect. IL-15 effect on HIV-1 in PBMC was independent of endogenous cytokine production. However, in Kit 225-K6, neutralizing antibodies to IL-7 had a significant effect on HIV-1 expression. These data suggest that IL-2, IL-12, and IL-15 increase HIV-1 replication predominantly through a posttranscriptional mechanism that may be enhanced by endogenous cytokine production.
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PMID:Induction of HIV-1 replication by type 1-like cytokines, interleukin (IL)-12 and IL-15: effect on viral transcriptional activation, cellular proliferation, and endogenous cytokine production. 953 56

This article reviews developments over nearly 15 years in the application of interferon-alpha (IFN-alpha) to the treatment of Kaposi's sarcoma (KS) in patients with acquired immunodeficiency syndrome (AIDS). The initial success of IFN treatment for selected patients with AIDS-associated KS occurred before identification of the human immunodeficiency virus (HIV) and in the absence of any coherent view of KS pathogenesis. A more comprehensive understanding of the biology of both AIDS and KS, together with increased knowledge of the biologic effects of IFN and therapeutic advances in the treatment of HIV infection, have made IFN therapy for KS both more rational and more successful. There is every reason to believe that the current results with IFN for KS can be improved on by capitalizing on recent improvements in HIV therapy and the availability of specific inhibitors of angiogenic cytokines. I sincerely thank the Milstein family and my colleagues in the International Society for Interferon and Cytokine Research (ISICR) for recognizing this work, which is the product of many collaborations between clinical and basic scientists in my own institution and elsewhere.
J Interferon Cytokine Res 1998 Apr
PMID:Interferon-alpha: evolving therapy for AIDS-associated Kaposi's sarcoma. 956 21

Macrophages recognize and are activated by unmethylated CpG motifs in bacterial DNA. Here we demonstrate that production of nitric oxide (NO) from murine RAW 264 macrophages and bone marrow-derived macrophages (BMM) in response to bacterial DNA is absolutely dependent on interferon-gamma (IFN-gamma) priming. Similarly, arginine uptake and expression of the inducible nitric oxide synthase (iNOS) gene in response to bacterial DNA in BMM occurred only after IFN-gamma priming. In contrast, mRNA for the cationic amino acid transporter, CAT2, was induced by plasmid DNA alone, and priming with IFN-gamma had no effect on this response. Tumor necrosis factor-alpha (TNF-alpha) release from RAW 264 and BMM in response to bacterial DNA was augmented by IFN-gamma pretreatment. In a stably transfected HIV-1 long terminal repeat (LTR) luciferase RAW 264 cell line, IFN-gamma and bacterial DNA synergized in activation of the HIV-1 LTR. Bacterial DNA has been shown to induce IFN-gamma production in vivo as an indirect consequence of interleukin-12 (IL-12) and TNF-alpha production from macrophages. The results herein suggest the existence of a self-amplifying loop that may have implications for therapeutic applications of bacterial DNA.
J Interferon Cytokine Res 1998 Apr
PMID:IFN-gamma primes macrophage responses to bacterial DNA. 956 29

Interleukin-1 (IL-1) produced in peripheral blood mononuclear cell (PBMC) cultures or added exogenously has been shown to upregulate HIV expression in vitro. Inhibition of IL-1 in HIV-infected individuals may inhibit HIV activation and slow disease progression. Recombinant human IL-1 receptor (rHu-IL-1R), the soluble extracellular portion of the human type I IL-1 receptor, inhibits HIV expression in acutely infected primary PBMCs and in the chronically infected promonocytic cell line, U1. We, therefore, conducted a phase I/II trial of the soluble rHu-IL-1R in HIV-1-infected individuals with CD4 T cell counts <300/microl to evaluate its safety and activity. Twelve evaluable patients were enrolled at three rHu-IL-1R dose levels:125 (n=3), 500 (n=3), and 1250 (n=6) microg/m2 per dose by subcutaneous (s.c.) injection three times a week for 8 weeks, followed by a 4 week observation period. rHu-IL-1R was safe and well tolerated. There were no deaths, no treatment-related grade 3/4 events, and no premature study discontinuations because of adverse events. The maximum tolerated dose was not reached. Seven patients reported improvements in one or more symptoms, including weight gain (3), improved energy level (4), decreased diarrhea (1), decreased night sweats (1), improvement in psoriatic arthritis (1), and improvement in a nonspecific chronic diffuse skin rash (1). Of 3 evaluable patients with Kaposi's sarcoma, 1 remained stable and 2 showed minimal progression. No consistent trends in absolute CD4 counts or percentages, quantitative HIV cultures, or serum p24 antigen, beta2-microglobulin, or triglyceride levels were observed. rHu-IL-1R is safe and well tolerated at the doses tested but induced no consistent changes in objective markers of HIV disease. Symptomatic improvements will require confirmation in randomized, placebo-controlled trials.
J Interferon Cytokine Res 1998 May
PMID:Phase I/II trial of the type I soluble recombinant human interleukin-1 receptor in HIV-1-infected patients. 962 Mar 59


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