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)

Central nervous system (CNS) involvement is a prominent feature of human immunodeficiency virus (HIV-1) infection. Monocytes and CD4+ T cells traverse the blood brain barrier (BBB), and serve as vehicles for the virus and perpetrators for brain pathology by their production of neurotoxins. In the present study cerebrospinal fluid (CSF) samples from HIV-1-infected patients were analyzed for the presence of chemotactic factors. All 36 CSF samples from the patients were positive for the CXC chemokine interferon-gamma inducible protein (IP-10), which was not detected in CSF samples of 14 controls. The IP-10 concentrations were higher in HIV-1-infected patients with HIV-1 associated neurologic disorders than in those without neurological deficits. In contrast to IP-10, other chemotactic factors including the CC chemokines MCP-1, MIP-1alpha, MIP-1beta and RANTES and the cytokines IL-15 and IL-16 were either not detected or increased in only less than 30% of the patients. Unlike the CSF samples of controls, all CSF samples from HIV-1-infected patients induced chemotaxis of T cells activated with IL-2. The significance of IP-10 as a T cell chemotactic cytokine in HIV-1-infected CSF is shown by (1) the correlation of the IP-10 levels with the extent of T cell chemotaxis, (2) the neutralization of T cell chemotaxis by anti-IP-10 antibodies and (3) the correlation of the chemotactic response of CSF samples on activated T cells and the CSF white cell count in the patients. Our data provide evidence that IP-10 contributes to the accumulation of activated T cells in the CSF compartment in HIV-1-infected individuals.
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PMID:Identification of a T cell chemotactic factor in the cerebrospinal fluid of HIV-1-infected individuals as interferon-gamma inducible protein 10. 1037 81

Several recent reports have provided evidence that Nef enhances human immunodeficiency virus HIV infectivity, and in vitro experiments with the nef gene have demonstrated the possible role of Nef in modulating immune responses. Exogenous Nef has been demonstrated to induce proliferation of normal human peripheral blood mononuclear cells (PBMC) and to enhance HIV-1 replication. The aim of this study was to evaluate the biological mechanisms by which Nef, used as exogenous protein, modulates cellular activation. We showed that exogenous Nef protein induces the proliferation of unstimulated and suboptimally stimulated normal human PBMC, while it has no effect on the proliferation of optimally stimulated PBMC. Moreover, the activating effect of exogenous Nef on PBMC proliferation was associated with an increase of IFN-gamma, TNF-alpha, and IL-6 production, while, surprisingly, IL-2 production was not affected by Nef. More importantly we showed, for the first time, that Nef exerts its activating effects on PBMC proliferation through IL-15 synthesis induction by monocyte/macrophage population. In conclusion, we found that exogenous Nef protein (i) induces activation of normal PBMC, increasing their proliferative response; (ii) modulates cytokine production; (iii) exerts its activating effects through IL-15 synthesis induction; and (iv) exerts these effects entering monocyte/macrophages. Our results might suggest that Nef enhances the rate of viral replication by a novel mechanism involving the production of IL-15.
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PMID:Induction of interleukin-15 production by HIV-1 nef protein: a role in the proliferation of uninfected cells. 1038 25

The CD56+CD16+ natural killer (NK) cell population plays a crucial role in eliminating virus-infected cells and is diminished in HIV-infected individuals. This study examined the effects of exogenous interleukin (IL)-15 on proliferation and survival of CD56+ and CD16+ cells of HIV-infected individuals. When used at equivalent concentrations in vitro, IL-15 was more potent than IL-2 as a growth factor for CD56+ cells, as well as for CD16+ cells and also CD4+ and CD8+ T cells. Analysis of cell survival in etoposide-treated cultures indicated that IL-15 was also more potent than IL-2 as a survival factor for CD56+ cells by virtue of its greater ability to up-regulate bcl-2 expression. Although IL-15-induced proliferation of CD56+ cells was accompanied by increased apoptosis, IL-15 was more effective than IL-2 in increasing the representation of viable CD56+ cells in the peripheral blood mononuclear cell population, but less effective in increasing T cell representation. The immunotherapeutic potential of IL-15 appears superior to IL-2 in regard to expanding NK cell populations in HIV-infected individuals, but needs to be weighed against poorer increases in T cell populations.
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PMID:Enhanced survival and potent expansion of the natural killer cell population of HIV-infected individuals by exogenous interleukin-15. 1042 44

IL-15 shares many biological properties with IL-2, a cytokine whose administration to HIV-infected individuals has been effective in enhancing depleted CD4 T lymphocyte numbers. The present study examined whether exogenous IL-15 could protect lymphocytes of HIV-infected individuals from spontaneous apoptosis, associated with growth factor deprivation, and CD95-induced apoptosis, which is believed to play a major role in T lymphocyte loss and HIV pathogenesis. Although IL-15, like IL-2, failed to inhibit CD95-induced lymphocyte apoptosis in vitro, IL-15 was found to act as a potent survival factor in the prevention of spontaneous apoptosis. The greater enhancement of lymphocyte survival, promoted by IL-15 as compared with IL-2 when used at an equivalent concentration, was associated with higher up-regulation of bcl-2 expression. In addition, IL-15 was more potent than IL-2 in stimulating lymphocyte proliferation. Despite the strong ability of IL-15 to promote both lymphocyte survival and proliferation, the increases in representation and total numbers of viable cells induced by IL-15 were not higher than those induced by IL-2. This appears to be associated with the greater ability of IL-15 to activate lymphocytes and increase their apoptosis-susceptibility. Therefore, lymphocyte loss occurring by growth factor deprivation in HIV infection may be potentially prevented by IL-15, although its benefits for survival need to be closely assessed against its ability to augment lymphocyte activation.
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PMID:Interleukin-15 is a potent survival factor in the prevention of spontaneous but not CD95-induced apoptosis in CD4 and CD8 T lymphocytes of HIV-infected individuals. Correlation with its ability to increase BCL-2 expression. 1055 78

Human herpesvirus 7, reported in 1990 is a lymphotropic member of the betaherpesvirus subfamily of herpesviruses. The virus is highly seroprevalent, primary infection usually occurs during childhood, and it has been associated with cases of exanthem subitum, pityriasis rosea, neurological manifestations and transplant complications. The latter two may warrant antiviral intervention, in vitro studies have shown that HHV-7 is susceptible to several nucleoside phosphonate compounds. In vitro, the virus has approximately a 5 day growth cycle in cultured lymphocytes; in vivo, latency is established in peripheral blood T-cells and a persistent infection is established in salivary gland tissue from which infectious virus is constitutively shed in saliva. The HHV-7 genome is approximately 145 kb and encodes at least 84 different proteins. Studies characterising HHV-7 gene products and the required interactions between viral and cellular genes necessary for virus replication, persistence and latency are in their infancy. HHV-7 infection has a variety of effects on host cells including upregulation of interleukin 15 and down-modulation of the cell surface molecule CD4; the latter serves as the cellular membrane receptor for HHV-7. Since HIV also infects T-cells via the CD4 molecule, the interactions of these viruses within T-cells during the course of AIDS are important areas of investigation.
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PMID:Human herpesvirus 7. 1057 20

One of the most characteristic and, at the same time, puzzling features of the cellular immune response towards HIV-1 is represented by an early vigorous HIV-specific CD8+ CTL response that does not prevent disease progression in the vast majority of patients. In this context, there is a striking mismatch over the course of disease progression between increasing numbers of activated CD8+ T cells and apparent decrease of virus-specific CD8+ CTLs. Inhibitory NK receptors (iNKRs) specific for HLA class I molecules can be expressed on CD8+ T-cells of healthy individuals and deliver inhibitory signals that determine decreased CTL function. Their expression on CD8+ CTL may be induced by IL-15 or TGFP in vitro, and may represent an important regulatory function for the fine-tuning of the antigen-specific T cell response against tumors and intracytoplasmic pathogens. In HIV-1 infected patients, relevant proportions of peripheral blood CD8+ T lymphocytes express iNKRs belonging to the Ig superfamily (p58/p70/p140) and CD94/NKG2A. Presence of iNKRs on CD8+ CTLs impairs HIV-1-specific cytolytic activity in vitro and may allow uncontrolled viral replication and spread following functional inhibition of CTL effectors in infected patients.
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PMID:HLA-class I-specific inhibitory receptors in HIV-1 infection. 1065 80

Type I interferons (IFNs) are cytokines exhibiting antiviral and antitumor effects, including multiple activities on immune cells. However, the importance of these cytokines in the early events leading to the generation of an immune response is still unclear. Here, we have investigated the effects of type I IFNs on freshly isolated granulocyte/macrophage colony-stimulating factor (GM-CSF)-treated human monocytes in terms of dendritic cell (DC) differentiation and activity in vitro and in severe combined immunodeficiency mice reconstituted with human peripheral blood leukocytes (hu-PBL-SCID) mice. Type I IFNs induced a surprisingly rapid maturation of monocytes into short-lived tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-expressing DCs endowed with potent functional activities, superior with respect to the interleukin (IL)-4/GM-CSF treatment, as shown by FACS((R)) analyses, mixed leukocyte reaction assays with allogeneic PBLs, and lymphocyte proliferation responses to HIV-1-pulsed autologous DCs. Type I IFN induced IL-15 production and strongly promoted a T helper cell type 1 response. Notably, injection of IFN-treated HIV-1-pulsed DCs in SCID mice reconstituted with autologous PBLs resulted in the generation of a potent primary immune response, as evaluated by the detection of human antibodies to various HIV-1 antigens. These results provide a rationale for using type I IFNs as vaccine adjuvants and support the concept that a natural alliance between these cytokines and monocytes/DCs represents an important early mechanism for connecting innate and adaptive immunity.
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PMID:Type I interferon as a powerful adjuvant for monocyte-derived dendritic cell development and activity in vitro and in Hu-PBL-SCID mice. 1081 70

In the present study, we show that IL-2, IL-4, IL-7, and IL-15 are able to induce functional CXCR4 surface expression on resting in vitro-generated CD4+ CXCR4- CCR7+ memory T cells. Cytokine-mediated induction of CXCR4 expression was associated with an increase in CXCR4 transcription, enhanced stromal-derived factor-1-induced T cell migration in vitro, and increased susceptibility of these cells to infection with X4 strains of HIV-1. CXCR4 expression could also be induced through an alternative pathway, following coculture of these cells with CD40-activated, autologous, CD34+ progenitor-derived dendritic cells. Although these dendritic cells express transcripts for IL-7 and IL-15, addition of neutralizing anti-IL-7R and IL-15 mAbs did not block induction of CXCR4 expression. Indeed, dendritic cell-mediated up-regulation of CXCR4 expression was found to depend on CD40/CD154 and CD134/CD134L interactions. Whereas activated autologous dendritic cells induced the expression of both CXCR4 and CD25 on a portion of CCR7+ memory T cells, concomitant CD3-mediated activation of these cells further enhanced CD25 expression, but, in contrast, prevented induction of CXCR4 expression. This observation suggests that triggering of the CD134 and CD154 molecules, in contrast to TCR/CD3 complex-mediated stimulation, results in simultaneous T cell activation and CXCR4 expression. Taken together, these results show that common gamma-chain-interacting cytokines as well as signals mediated via noncognate interactions between activated dendritic cells and memory T cells are involved in the up-regulation of CXCR4 expression.
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PMID:Cytokines and cell surface molecules independently induce CXCR4 expression on CD4+ CCR7+ human memory T cells. 1087 44

It has been suggested that CD4+ T cell proliferative responses to HIV p24 Ag may be important in the control of HIV infection. However, these responses are minimal or absent in many HIV-infected individuals. Furthermore, while in vitro and in vivo responses to non-HIV recall Ags improve upon administration of highly active antiretroviral therapy, there does not appear to be a commensurate enhancement of HIV-specific immune responses. It is possible that CD4+ p24-specific T cells are deleted early in the course of infection. However, it is also possible that a discrete unresponsiveness, or anergy, contributes to the lack of proliferation to p24. To evaluate the possible contribution of unresponsiveness to the lack of CD4+ T cell proliferation to p24 in HIV-infected individuals, we attempted to overcome unresponsiveness. CD40 ligand trimer (CD40LT) and IL-12 significantly increased PBMC and CD4+ T cell proliferative responses to p24 Ag in HIV-infected, but not uninfected, individuals. No increase in proliferative response to CMV Ag was observed. CD40LT exerted its effect through B7-CD28-dependent and IL-12- and IL-15-independent mechanisms. Finally, the increase in proliferation with CD40LT and IL-12 was associated with an augmented production of IFN-gamma in most, but not all, individuals. These data suggest the possible contribution of HIV-specific unresponsiveness to the lack of CD4+ T cell proliferation to p24 Ag in HIV-infected individuals and that clonal deletion alone does not explain this phenomenon. They also indicate the potential for CD40LT and IL-12 as immune-based therapies for HIV infection.
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PMID:CD40 ligand trimer and IL-12 enhance peripheral blood mononuclear cells and CD4+ T cell proliferation and production of IFN-gamma in response to p24 antigen in HIV-infected individuals: potential contribution of anergy to HIV-specific unresponsiveness. 1090 80

Polymorphonuclear leukocyte (PMN) dysfunction has been reported in human immunodeficiency virus (HIV)-infected patients. Interleukin (IL)-15 is a recently discovered cytokine that potentiates antimicrobial functions of normal PMNs. We evaluated the in vitro effect of IL-15 on chemotaxis and fungicidal activity of PMNs from 9 patients with untreated advanced HIV infection, 8 patients with viral suppression after 52 to 130 weeks of highly active antiretroviral therapy (HAART), and 12 patients with treatment failure. We also studied oxidative burst and apoptosis of PMNs in 5 patients with untreated advanced HIV infection. Twelve healthy donors were included as controls. Chemotaxis and fungicidal activity of unprimed PMNs was significantly lower in patients with untreated HIV infection compared with controls. After incubation with IL-15, a significant increase in PMN chemotaxis and fungicidal activity was found; moreover, IL-15 induced a significant reduction in the number of apoptotic HIV(+) PMNs. IL-15 did not modulate oxidative burst of HIV(+) PMNs as measured by chemiluminescence production. The in vitro priming of PMNs with IL-15 determined a complete reversal of defective chemotaxis and killing in all HAART-treated patients with long-term HIV suppression. IL-15 significantly enhanced chemotaxis and fungicidal activity also in patients with HAART failure. In conclusion, IL-15 is an important cytokine in the activation of the functional properties of HIV(+) PMNs, by delaying apoptosis and enhancing chemotaxis and fungicidal activity. The potent stimulant effect of IL-15 on PMN function was observed in antiretroviral naive patients as well as in individuals who were receiving HAART, including those with treatment failure. (Blood. 2000;96:1979-1984)
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PMID:Interleukin-15 enhances neutrophil functional activity in patients with human immunodeficiency virus infection. 1096 3


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