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

The productive infection of human monocyte-derived macrophages (Mphi) by HIV was suppressed by primary CD8+ cells from asymptomatic HIV-infected individuals. This anti-HIV response was noncytotoxic; removal of the CD8+ cells from the infected Mphi leads to virus production. CD8+ cells inhibited HIV replication when separated from the infected Mphi by a transwell filter insert, indicating a diffusible factor made by the CD8+ cells suppressed productive infection of Mphi. Three beta-chemokines, which can be secreted by activated CD8+ cells, RANTES (regulated on activation normal T cell expressed and secreted), macrophage inflammatory protein (MIP)-1alpha and MIP-1beta prevented HIV replication in the Mphi cultures. In addition, incubation of acutely infected Mphi with a mixture of neutralizing antibodies to RANTES, MIP-1alpha, and MIP-1beta enhanced virus replication. Nevertheless, neutralization of beta-chemokines with specific antibodies did not abolish the suppression by CD8+ cells of HIV replication in Mphi. Thus, even though beta-chemokines decrease HIV replication in Mphi, these cytokines are not responsible for the ability of CD8+ cells to inhibit HIV production in these cells.
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PMID:Primary CD8+ cells from HIV-infected individuals can suppress productive infection of macrophages independent of beta-chemokines. 946 84

Macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, and RANTES production were measured by ELISA in whole blood that had been stimulated for 4.5 h with phytohemagglutinin. The blood was from 90 healthy human immunodeficiency virus (HIV)-negative controls and from 245 HIV-infected subjects who were followed for < or = 4.5 years. HIV-infected persons without AIDS had increased levels of MIP-1alpha, MIP-1beta, and RANTES (P < .01) compared with levels in controls. Subjects with AIDS, compared with controls, had decreased production levels of MIP-1beta (P < .0001) and similar levels of MIP-1alpha and RANTES. A high level of MIP-1beta production was associated with a decreased risk of progressing to AIDS or death, as determined by univariate analysis (P < .01) and adjusted for CD4 cell count and age (P = .07, P = .06, respectively). The findings suggest that the production level of beta-chemokine changes during HIV infection and that a high level of beta-chemokine production in peripheral blood lymphocytes may be associated with less rapid disease progression in HIV infection.
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PMID:Production of beta-chemokines in human immunodeficiency virus (HIV) infection: evidence that high levels of macrophage inflammatory protein-1beta are associated with a decreased risk of HIV disease progression. 946 18

Human immunodeficiency virus, type I (HIV-1) cell-type tropism is dictated by chemokine receptor usage: T-cell line tropic viruses use CXCR4, whereas monocyte tropic viruses primarily use CCR5 as fusion coreceptors. CC chemokines macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, and RANTES (regulated on activation normal T cell expressed and secreted) inhibit CD4/CCR5-mediated HIV-1 cell fusion. MCP-2 is also a member of the CC chemokine subfamily and has the capacity to interact with at least two receptors including CCR-1 and CCR2B. In an effort to further characterize the binding properties of MCP-2 on leukocytes, we observed that MCP-2, but not MCP-1, effectively competed with MIP-1beta for binding to monocytes, suggesting that MCP-2 may interact with CCR5. As predicted, MCP-2 competitively inhibited MIP-1beta binding to HEK293 cells stably transfected with CCR5 (CCR5/293 cells). MCP-2 also bound to and induced chemotaxis of CCR5/293 cells with a potency comparable with that of MIP-1beta. Confocal microscopy indicates that MCP-2 caused remarkable and dose-dependent internalization of CCR5 in CCR5/293 cells. Furthermore, MCP-2 inhibited the entry/replication of HIV-1ADA in CCR5/293 cells coexpressing CD4. These results indicated that MCP-2 uses CCR5 as one of its functional receptors and is an additional potent natural inhibitor of HIV-1.
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PMID:Monocyte chemotactic protein-2 activates CCR5 and blocks CD4/CCR5-mediated HIV-1 entry/replication. 946 73

The beta-chemokines RANTES, MIP-1alpha, and MIP-1beta have been shown to inhibit the infection of T cells by macrophage-tropic HIV-1 strains by blocking env-driven HIV-1 fusion through competition for the chemokine receptors or receptor downregulation. This study was aimed at testing whether beta-chemokines also inhibit the productive infection of monocyte-derived macrophages (MDMs) by a monocytotropic HIV-1 strain, by using virus yield assays. The action of the beta-chemokines MIP-1alpha, MIP-1beta, and RANTES was captured with that of the alpha-chemokine interleukin 8 (IL-8) and of interferon alpha (IFN-alpha), which is a well-known broad-range inhibitor of viral replication. While IL-8 did not inhibit HIV-1 BaL replication in MDMs, the beta-chemokines were dose-dependently inhibitory. RANTES was the most effective, reaching at 300 ng/ml a protection similar to that obtained with IFN-alpha at 1000 IU/ml, and was even more inhibitory when added to MDMs after virus attachment. In contrast to IFN-alpha, the antiviral activity of beta-chemokines was restricted to HIV, because another virus was not inhibited. As compared with untreated MDMs, full-length proviral DNA at day 1 postinfection was inhibited in MDMs treated with RANTES either before or after the absorption phase, and even more so in IFN-treated MDMs, whereas in IL-8-treated MDMs no inhibition was observed. Our results indicate that in MDMs both RANTES and IFN affect early steps of HIV-1 BaL replication, preceding the completion of viral DNA synthesis.
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PMID:Inhibition of HIV type 1 BaL replication by MIP-1alpha, MIP-1beta, and RANTES in macrophages. 949 13

Human immunodeficiency virus type 1 (HIV-1) uses a variety of chemokine receptors as coreceptors for virus entry, and the ability of the virus to be neutralized by antibody may depend on which coreceptors are used. In particular, laboratory-adapted variants of the virus that use CXCR4 as a coreceptor are highly sensitive to neutralization by sera from HIV-1-infected individuals, whereas primary isolates that use CCR5 instead of, or in addition to, CXCR4 are neutralized poorly. To determine whether this dichotomy in neutralization sensitivity could be explained by differential coreceptor usage, virus neutralization by serum samples from HIV-1-infected individuals was assessed in MT-2 cells, which express CXCR4 but not CCR5, and in mitogen-stimulated human peripheral blood mononuclear cells (PBMC), where multiple coreceptors including CXCR4 and CCR5 are available for use. Our results showed that three of four primary isolates with a syncytium-inducing (SI) phenotype and that use CXCR4 and CCR5 were neutralized poorly in both MT-2 cells and PBMC. The fourth isolate, designated 89.6, was more sensitive to neutralization in MT-2 cells than in PBMC. We showed that the neutralization of 89.6 in PBMC was not improved when CCR5 was blocked by having RANTES, MIP-1alpha, and MIP-1beta in the culture medium, indicating that CCR5 usage was not responsible for the decreased sensitivity to neutralization in PBMC. Consistent with this finding, a laboratory-adapted strain of virus (IIIB) was significantly more sensitive to neutralization in CCR5-deficient PBMC (homozygous delta32-CCR5 allele) than were two of two SI primary isolates tested. The results indicate that the ability of HIV-1 to be neutralized by sera from infected individuals depends on factors other than coreceptor usage.
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PMID:Evidence that antibody-mediated neutralization of human immunodeficiency virus type 1 by sera from infected individuals is independent of coreceptor usage. 949 40

Selective leukocyte trafficking towards sites of inflammation is mediated by chemokines. RANTES is a CC chemokine that attracts lymphocytes, monocytes, dendritic cells, eosinophils, basophils and NK cells. A natural form of human RANTES lacking two N-terminal residues was isolated from stimulated sarcoma cells, fibroblasts, and leukocytes. RANTES(3-68) showed a more than tenfold reduction in chemotactic potency for monocytes and eosinophils. To elucidate the mechanism involved, receptor recognition studies were performed. In cells transfected with the CC chemokine receptor (CCR) 5, the major co-receptor for macrophage-tropic HIV-1 strains, RANTES(3-68) mobilized calcium and desensitized RANTES(1-68)-induced calcium fluxes equally well as RANTES(1-68). However, RANTES(3-68) was ineffective on CCR1 and CCR3 transfectants. The reduced potency of natural RANTES(3-68) by selective loss of receptor-activating characteristics was confirmed with recombinant RANTES(3-68). In chemotaxis assays using monocytic cells, RANTES(3-68) inhibited RANTES(1-68), macrophage inflammatory protein-1alpha (MIP-1alpha), MIP-1beta or monocyte chemotactic protein-3 (MCP-3), but not MCP-1- or MCP-2-induced chemotaxis. Thus, a minor post-translational modification has a remarkable impact on the biological activities of RANTES and a pathophysiologically induced change in the relative amounts of intact and truncated RANTES might affect the outcome of inflammation or HIV infection.
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PMID:Natural truncation of RANTES abolishes signaling through the CC chemokine receptors CCR1 and CCR3, impairs its chemotactic potency and generates a CC chemokine inhibitor. 956 66

CD8+ T lymphocytes from HIV+ individuals can potently suppress HIV-1 replication in a noncytolytic manner. This suppression appears to be multifactorial and the molecules contributing have not been fully elucidated. As an approach to this question we used herpesvirus saimiri (HVS) to transform CD8+ T lymphocytes from an HIV+ asymptomatic donor to a continuously growing, activation-independent, IL-2-dependent phenotype. The transformed cell population, termed CD8(HVS), had an activated phenotype, contained HVS sequences, did not shed infectious HVS virus, and was polyclonal. The CD8(HVS) cells, despite the absence of detectable CTL activity, potently suppressed HIV-1 production by both autologous and heterologous CD4+ cells from infected donors. The CD8(HVS) cells in coculture also suppressed virus production from PBMCs acutely infected with syncytium-inducing (SI) strains or NSI primary isolates of HIV-1. The supernatants from the CD8(HVS) cells and their concentrates derived from these supernatants were suppressive to NSI primary isolates of HIV-1 but not to SI strains. Fractionation of these concentrates showed that the suppressive activity was associated with low molecular mass (6500- to 19,300-Da) protein species. Western blotting and ELISA indicated that the CC chemokines MIP-1alpha, MIP-1beta, and RANTES were present in these fractions. Antibody-blocking studies with antibodies to the CC chemokines indicated that a significant portion of the soluble HIV-suppressive activity was due to these molecules. However, these experiments also suggested the inhibitory activity of the CD8(HVS) cells in coculture is not due exclusively to the CC chemokines. The HVS-transformed cells provide a useful tool for the study of noncytolytic CD8+ T lymphocyte-mediated suppression of HIV-1.
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PMID:Herpesvirus saimiri transformation of HIV type 1 suppressive CD8+ lymphocytes from an HIV type 1-infected asymptomatic individual. 956 55

The in vivo response of the immune system after HIV infection in regard to cytokine production and C-C chemokine synthesis is not well known. Here we have analysed cytokine and chemokine mRNA production in lymph nodes with follicular hyperplasia (FHLN) of HIV-infected patients by in situ hybridization using anti-sense mRNA probes. The synthesis of mRNAs for interferon-gamma (IFN-gamma), IL-12p35, IL-12p40, IL-4, and for the C-C chemokines RANTES, MIP-1alpha, and MIP-1beta was compared with that of lymph nodes from non-infected individuals to define HIV-specific events. Only few cells expressing IFN-gamma, RANTES, MIP-1alpha, and MIP-1beta mRNAs were detectable in the T-dependent area of lymph nodes from HIV-negatives. In contrast, in FHLN from HIV+ patients a high number of IFN-gamma, RANTES, MIP-1alpha, and MIP-1beta mRNA-containing cells were detectable. Remarkably, only single individual IL-12p35 mRNA-producing cells were present in the T-dependent area from both HIV+ and HIV lymph nodes. Furthermore, the low number of IL-12p40 mRNA-expressing cells did not differ between HIV+ and HIV- lymph nodes. This indicates that IFN-gamma is expressed independently of IL-12, possibly by a direct T cell-mediated reaction. IL-4 mRNA-producing cells were hardly detectable in infected and control lymph nodes. The same findings were made in a limited number of samples from patients with advanced disease. Thus, these results demonstrate that a high IFN-gamma production is accompanied by a strong expression of MIP-1alpha, MIP-1beta, and RANTES in the lymph node after HIV infection. This favours the idea that a Th1-type immune response correlates with a preferential production of C-C chemokines in FHLN of HIV+ patients.
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PMID:Expression of macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, and RANTES genes in lymph nodes from HIV+ individuals: correlation with a Th1-type cytokine response. 956 95

The CC chemokines MIP-1alpha, MIP-1beta, and RANTES suppress replication of certain HIV-1 strains in cultured PBMC and T cell lines by blocking interaction of gp120 with CC chemokine receptor 5 (CCR5). However, the same chemokines can enhance HIV-1 replication in cultured macrophages. The net effect of chemokines on HIV-1 infection in intact lymphoid tissue, the major reservoir of HIV-1 in vivo, is unknown and unpredictable since the tissue contains both T lymphocytes and macrophages. Here we show that exogenous MIP-1alpha, MIP-1beta, and RANTES markedly suppressed replication of CCR5-tropic HIV-1 strains in blocks of human lymphoid tissue infected ex vivo. Moreover, endogenous MIP-1alpha, MIP-1beta, and RANTES were upregulated in tissues infected ex vivo with CXC chemokine receptor 4-tropic but not CCR5-tropic HIV-1. Such an upregulation may contribute to the virus phenotype shift in the course of HIV disease in vivo.
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PMID:Blockade of CC chemokine receptor 5 (CCR5)-tropic human immunodeficiency virus-1 replication in human lymphoid tissue by CC chemokines. 957 51

We examined the human immunodeficiency virus type 1 infectability of CD4+ lymphocytes isolated from CCR5 wild-type individuals, individuals heterozygous for the delta32 allele of CCR5, and HIV-1-exposed but uninfected (EU) individuals who had CD4+ lymphocytes refractory to M-tropic viral replication. None of the EU individuals were found to be heterozygous for the delta32 allele. The CD4+ lymphocytes isolated from CCR5/delta32 and EU individuals were less infectable with an M-tropic viral isolate of HIV-1 than CCR5/CCR5 control individuals but were equally as infectable with a T-tropic viral isolate. The restriction to M-tropic viral isolate replication did not associate with any profound genotypic change in the CCR5 gene. CD4+ lymphocytes from CCR5/delta32 and CCR5/CCR5 EU individuals were more sensitive to the HIV-inhibitory effects of the recombinant beta-chemokines RANTES, MIP-1alpha, and MIP-1beta than were CD4+ lymphocytes from CCR5/CCR5 control individuals. CD4+ lymphocytes from EU individuals also showed increased sensitivity to recombinant beta-chemokines and low surface expression of CCR5. A phenotype of low CCR5 expression and high secretion of beta-chemokines is associated with reduced infectability of cells by M-tropic HIV-1. This phenotype may also be associated with protection against sexual transmission of HIV-1.
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PMID:Reduced HIV-1 infectability of CD4+ lymphocytes from exposed-uninfected individuals: association with low expression of CCR5 and high production of beta-chemokines. 958 79


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