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

The ability of CD8 T cells derived from human immunodeficiency virus (HIV)-infected patients to produce soluble HIV-suppressive factor(s) (HIV-SF) has been suggested as an important mechanism of control of HIV infection in vivo. The C-C chemokines RANTES, MIP-1 alpha and MIP-1 beta were recently identified as the major components of the HIV-SF produced by both immortalized and primary patient CD8 T cells. Whereas they potently inhibit infection by primary and macrophage-tropic HIV-1 isolates, T-cell line-adapted viral strains tend to be insensitive to their suppressive effects. Consistent with this discrepancy, two distinct chemokine receptors, namely, CXCR4 (ref. 7) and CCR5 (ref. 8), were recently identified as potential co-receptors for T-cell line-adapted and macrophage-tropic HIV-1 isolates, respectively. Here, we demonstrate that the third hypervariable domain of the gp 120 envelope glycoprotein is a critical determinant of the susceptibility of HIV-1 to chemokines. Moreover, we show that RANTES, MIP-1 alpha and MIP-1 beta block the entry of HIV-1 into cells and that their antiviral activity is independent of pertussis toxin-sensitive signal transduction pathways mediated by chemokine receptors. The ability of the chemokines to block the early steps of HIV infection could be exploited to develop novel therapeutic approaches for AIDS.
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PMID:The V3 domain of the HIV-1 gp120 envelope glycoprotein is critical for chemokine-mediated blockade of infection. 909 60

Seven of 112 hemophiliacs infected with human immunodeficiency virus type-1 (HIV-1) before 1986 through contaminated plasma products are currently healthy, with CD4 T-cell counts above 500 cells/microL, and have never received antiretroviral therapy (long-term nonprogressors [LTNPs]). Seven age and sex-matched hemophiliacs infected in the same period but who have progressive HIV disease (progressors) and one additional slow-progressing individual were also studied. One hundred-fold, 20-fold, and 10-fold lower levels of full-length HIV RNA in plasma, peripheral blood mononuclear cells (PBMCs), and proviral DNA in PBMCs, respectively, were found in LTNPs compared with progressors. Plasma and cell-associated HIV RNA and proviral DNA were lower in LTNPs who tested negative for viral isolation from PBMCs or who were positive only after removal of CD8+ cells. No substantial differences were observed in the in vitro production of chemokines including RANTES, MIP-1 alpha, MIP-1 beta, MCP-1, and interleukin-8 (IL-8) in supernatants of activated PBMCs or CD8-depleted PBMCs of LTNPs, even when HIV isolation was simultaneously accomplished exclusively after removal of CD8+ cells. Low levels of HIV load and replication in peripheral blood are the strongest correlates of nonprogression in this small number of infected hemophiliacs.
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PMID:Hemophilia and nonprogressing human immunodeficiency virus type 1 infection. 932 56

It has been demonstrated that CD8+ T cells produce a soluble factor(s) that suppresses human immuno-deficiency virus (HIV) replication in CD4+ T cells. The role of soluble factors in the suppression of HIV replication in monocyte/macrophages (M/M) has not been fully delineated. To investigate whether a CD8+ T-cell-derived soluble factor(s) can also suppress HIV infection in the M/M system, primary macrophages were infected with the macrophage tropic HIV-1 strain Ba-L. CD8+ T-cell-depleted peripheral blood mononuclear cells were also infected with HIV-1 IIIB or Ba-L. HIV expression from the chronically infected macrophage cell line U1 was also determined in the presence of CD8+ T-cell supernatants or beta-chemokines. We demonstrate that: (i) CD8+ T-cell supernatants did, but beta-chemokines did not, suppress HIV replication in the M/M system; (ii) antibodies to regulated on activation normal T-cell expressed and Secreted (RANTES), macrophage inflammatory protein 1 alpha (MIP-1 alpha) and MIP-1 beta did not, whereas antibodies to interleukin 10, interleukin 13, interferon alpha, or interferon gamma modestly reduced anti-HIV activity of the CD8+ T-cell supernatants; and (iii) the CD8+ T-cell supernatants did, but beta-chemokines did not, suppress HIV-1 IIIB replication in peripheral blood mononuclear cells as well as HIV expression in U1 cells. These results suggest that HIV-suppressor activity of CD8+ T cells is a multifactorial phenomenon, and that RANTES, MIP-1 alpha, and MIP-1 beta do not account for the entire scope of CD8+ T-cell-derived HIV-suppressor factors.
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PMID:CD8+ T-cell-derived soluble factor(s), but not beta-chemokines RANTES, MIP-1 alpha, and MIP-1 beta, suppress HIV-1 replication in monocyte/macrophages. 898 13

Primary HIV-1 isolates were evaluated for their sensitivity to inhibition by beta-chemokines RANTES (regulated upon activation, normal T-cell expressed and secreted), macrophage inflammatory protein 1 alpha (MIP-1 alpha), and MIP-1 beta. Virus isolates of both nonsyncytium-inducing (NSI) and syncytium-inducing (SI) biological phenotypes recovered from patients at various stages of HIV-1 infection were assessed, and the results indicated that only the isolates with the NSI phenotype were substantially inhibited by the beta-chemokines. More important to note, these data demonstrate that resistance to inhibition by beta-chemokines RANTES, MIP-1 alpha, and MIP-1 beta is not restricted to T cell line-adapted SI isolates but is also a consistent property among primary SI isolates. Analysis of isolates obtained sequentially from infected individuals in whom viruses shifted from NSI to SI phenotype during clinical progression exhibited a parallel loss of sensitivity to beta-chemokines. Loss of virus sensitivity to inhibition by beta-chemokines RANTES, MIP-1 alpha, and MIP-1 beta was furthermore associated with changes in the third variable (V3) region amino acid residues previously described to correlate with a shift of virus phenotype from NSI to SI. Of interest, an intermediate V3 genotype correlated with a partial inhibition by the beta-chemokines. In addition, we also identified viruses sensitive to RANTES, MIP-1 alpha, and MIP-1 beta of NSI phenotype that were isolated from individuals with AIDS manifestations, indicating that loss of sensitivity to beta-chemokine inhibition and shift in viral phenotype are not necessarily prerequisites for the pathogenesis of HIV-1 infection.
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PMID:Sensitivity to inhibition by beta-chemokines correlates with biological phenotypes of primary HIV-1 isolates. 898 20

Chemokines were originally characterized by their ability to direct migration and induce activation of selected leukocyte populations. The beta-chemokines MIP-1 alpha, MIP-beta, and RANTES have been implicated in the suppression of viral replication by CD8+ T cells from HIV-infected individuals. The present study was undertaken to evaluate the effect of beta-chemokines on HIV replication in cocultures of dendritic cells (DCs) and CD4+ T cells, and an in vitro model of the lymphoid microenvironment. In the acute infection system, where DCs from uninfected individuals are pulsed with HIV and cocultured with autologous CD4+ T cells, no inhibition of replication of monocytotropic or T cell tropic viral isolates by MIP-1 alpha, MIP-1 beta, and RANTES, alone or in combination, was observed. In contrast, in an endogenous infection system, where the DCs and CD4+ T cells were obtained from HIV-infected subjects, addition of recombinant beta-chemokines suppressed HIV replication. However, neutralizing antibodies to beta-chemokines did not affect the suppressive activity of CD8+ T cells from HIV-infected donors in either system, suggesting that CD8+ T cell-mediated suppression is not due exclusively to beta-chemokines. Furthermore, no significant differences in secretion of MIP-1 alpha, MIP-1 beta, and RANTES by purified CD8+ T cells were noted in uninfected versus HIV-infected donors, regardless of the stage of disease. These results indicate that HIV suppression by CD8+ T cells derived from HIV-infected donors is a multifactorial phenomenon and not limited to the action of MIP-1 alpha, MIP-1 beta, and RANTES.
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PMID:Multifactorial nature of noncytolytic CD8+ T cell-mediated suppression of HIV replication: beta-chemokine-dependent and -independent effects. 898 28

Evidence suggests that CD8+ lymphocytes are involved in the control of Human Immunodeficiency virus type 1 (HIV-1) infection by the release of HIV-suppressive factors. The human chemokines RANTES and the macrophage inflammatory protein 1 alpha (MIP-1 alpha) have been identified to be potent inhibitors of HIV in vitro. The aim of this study was to determine whether high levels of these chemokines are associated with a delayed progression of HIV disease. We have therefore analysed the in vitro production of RANTES and MIP-1 alpha from purified stimulated CD8+ cells from HIV+ long term survivors (LTS) and, as a comparison, from HIV+ patients with progressive disease. RANTES production was similar in LTS and progressors (14.06 +/- 3, 13.36 +/- 4.1 ng/ml, not statistically significant); the same cells from healthy controls show a RANTES production of 20 +/- 3.5 ng/ml (P = 0.034 versus LTS and P = 0.038 versus progressors). MIP-1 alpha production was slightly reduced in LTS (96.8 +/- 12 ng/ml) and progressors (91.6 + 17, not statistically significant between the two groups) when compared to healthy controls (109 +/- 7 ng/ml, P = 0.03). Our study suggests that resistance to HIV-1 progression in LTS may not be associated with high levels of RANTES and MIP-1 alpha production.
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PMID:CD8+ cells in HIV infection produce macrophage inflammatory protein-1 alpha and RANTES: a comparative study in long-term survivors and progressor patients. 902 86

The recent discovery of a chemokine receptor, fusin (fusin/CXCR-4), as the long-sought human immunodeficiency virus type 1 (HIV-1) coreceptor opened an entirely new field of aquired immunodeficiency syndrome (AIDS) research on mechanisms of viral entry, tropism and pathogenesis. It was soon followed by the identification of the chemokine receptor CCR-5 as the major macrophage-tropic (M-tropic) HIV-1 coreceptor and the demonstration that other chemokine receptors, CCR-3 and CCR-2b, also may serve as coreceptors, albeit at somewhat lower efficiency. Very recently it was demonstrated that the mechanism of the coreceptor function involves the formation of a complex on the cell surface between the HIV-1 envelope, the primary receptor CD4 and the coreceptor. Thus the prevention of the HIV-1 envelope glycoprotein-mediated fusion by the chemokines RANTES, macrophage inflammatory protein-1 alpha (MIP-1 alpha) and MIP-1 beta, as well as by the recently identified fusin/CXCR-4 ligand, stromal cell-derived factor-1 (SDF-1) could be explained by disruption of that complex. Interestingly, the identification of the HIV-1 coreceptor CCR-5 not only provided new insights into the mechanisms of viral entry and tropism, but also may help in explaining why some people with genetic alterations in CCR-5 are protected from HIV-1 infection.
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PMID:HIV and the 7-transmembrane domain receptors. 903 25

Human herpesvirus-8 (HHV-8) has been detected in Kaposi's sarcoma (KS) lesions of all types (AIDS-related, classical and endemic), in body-cavity-based B-cell lymphomas (BCBLs) and in lesions of multicentric Castleman's disease (MCD). We have identified a major gamma-herpesvirus-divergent locus (DL-B) in HHV-8 DNA encoding several HHV-8 unique open reading frames (ORFs), including a homologue of interleukin-6 (IL-6) and two homologues of macrophage inflammatory protein MIP-1. We show that the HHV-8-encoded IL-6 homologue (vIL-6) shares functional properties with endogenous IL-6 proteins and that both vIL-6 and vMIP-1 transcripts are present at high levels following butyrate induction of an HHV-8' BCBL cell line. Low amounts of constitutive vIL-6, but not vMIP-1, mRNA were also detected. The presence of a functional IL-6 homologue encoded by HHV-8 may provide a mechanistic model for the hypothesized role of HHV-8 in KS, MCD and BCBL that involves the mitogenic effects of vIL-6 on surrounding cells. MIP-1 proteins may enhance these effects through the chemotactic recruitment of endogenous cytokine-producing cells into affected tissues and could potentially influence HIV disease progression in coinfected individuals through interactions with the HIV co-receptor CCR-5.
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PMID:Kaposi's sarcoma-associated human herpesvirus-8 encodes homologues of macrophage inflammatory protein-1 and interleukin-6. 905 55

Herpesvirus saimiri (HVS), strain 488-77, was used to derive continuously growing transformed human CD8+ T cell lines that can suppress HIV replication in CD4+ cells via the production of an antiviral factor(s). Transformed CD8+ cell lines were obtained by HVS infection of peripheral blood mononuclear cells or purified CD8- T cells from HIV-infected or uninfected individuals. Suppression of primary or laboratory isolates of HIV was mediated by factor permeation of a transwell membrane or by cell-free culture supernatants. Suppressing and nonsuppressing cell lines were IL-2-dependent for good growth and showed a similar activated cell surface phenotype. The cell lines produced varying amounts of the cytokines IL-8, IL-10, TNF-alpha, TNF-beta, RANTES, MIP-1 alpha, and MIP-1 beta, but not IFN-alpha. No correlation was observed between the level of any of these cytokines and the presence or absence of antiviral activity in cell line culture supernatants. These cell lines have become an important resource for studying antiviral factors produced by CD8+ T cells from HIV-infected individuals.
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PMID:Derivation of herpesvirus saimiri-transformed CD8+ T cell lines with noncytotoxic anti-HIV activity. 907 51

Monocyte chemotactic proteins (MCPs) form a subfamily of chemokines that recruit leukocytes to sites of inflammation and that may contribute to tumor-associated leukocyte infiltration and to the antiviral state against HIV infection. With the use of degenerate primers that were based on CC chemokine consensus sequences, the known MIP-1 alpha/LD78 alpha, MCP-1, and MCP-3 genes and the previously unidentified eotaxin and MCP-2 genes were isolated from a YAC contig from human chromosome 17q11.2. The amplified genomic MCP-2 fragment was used to isolate an MCP-2 cosmid from which the gene sequence was determined. The MCP-2 gene shares with the MCP-1 and MCP-3 genes a conserved intron-exon structure and a coding nucleotide sequence homology of 77%. By Northern blot analysis the 1.0-kb MCP-2 mRNA was predominantly detectable in the small intestine, peripheral blood, heart, placenta, lung, skeletal muscle, ovary, colon, spinal cord, pancreas, and thymus. Transcripts of 1.5 and 2.4 kb were found in the testis, the small intestine, and the colon. The isolation of the MCP-2 gene from the chemokine contig localized it on YAC clones of chromosome 17q11.2, which also contain the-eotaxin, MCP-1, MCP-3, and NCC-1/MCP-4 genes. The combination of using degenerate primer PCR and YACs illustrates that novel genes can efficiently be isolated from gene cluster contigs with less redundancy and effort than the isolation of novel ESTs.
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PMID:The human MCP-2 gene (SCYA8): cloning, sequence analysis, tissue expression, and assignment to the CC chemokine gene contig on chromosome 17q11.2. 911


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