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

Two chemokine (chemoattractant cytokines) beta peptides, macrophage inflammatory proteins 1 alpha and 1 beta (MIP-1 alpha and MIP-1 beta), were induced in human monocyte cultures following infection with the human immunodeficiency virus type 1 (HIV-1). Induction depended on productive viral infection: not only did the kinetics of MIP-1 peptide induction closely follow those of viral replication, but monocyte cultures inoculated with heat-inactivated virus or infected in the presence of AZT failed to produce these chemokine beta peptides. In addition, HIV infection markedly altered the pattern of beta chemokine expression elicited by tumor necrosis factor (TNF), itself a potent proinflammatory cytokine upregulated during the development of AIDS. Reverse transcription (RT)-PCR and RT-in situ PCR studies on brain tissue from patients with AIDS dementia demonstrated elevated MIP-1 alpha and MIP-1 beta mRNA expression relative to comparable samples from HIV-1-infected patients without dementia. Cells expressing chemokines in HIV-1-infected brains were identified morphologically as microglia and astrocytes. As MIP-1 alpha and MIP-1 beta are potent chemoattractants for both monocytes and specific subpopulations of lymphocytes, this dysregulation of beta chemokine expression may influence the trafficking of leukocytes during HIV infection. These data, taken together, suggest a mechanism by which HIV-1-infected monocytes might recruit uninfected T cells and monocytes to sites of active viral replication or inflammation, notably the brain and lymph nodes.
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PMID:Human immunodeficiency virus type 1 infection alters chemokine beta peptide expression in human monocytes: implications for recruitment of leukocytes into brain and lymph nodes. 857 Jun 19

Recruitment of T lymphocytes to lymph nodes in patients with HIV infection is critical to the pathogenesis of disease. Chemokines are a family of cytokines, which are potent regulators of leukocyte migration. We studied the leukocyte populations and expression of chemokines known to be active upon T cells in lymph nodes of four HIV infected patients and seven control subjects using in situ hybridization, immunohistochemistry, and FACS analysis. The HIV lymph nodes showed CD8+ T lymphocyte accumulation and strongly enhanced chemokine expression, notably for the CD8+ T cell chemoattractant, macrophage inflammatory protein (MIP)-1 alpha. Resident macrophages appeared to be a major cellular source of chemokines in the HIV nodes. RANTES expression was present in both HIV and control lymph nodes, suggesting a physiological role for this chemokine in T lymphocyte recirculation. Chemokines may be important determinants of T lymphocyte accumulation in lymphoid tissue of patients with HIV/AIDS.
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PMID:Chemokines and T lymphocyte recruitment to lymph nodes in HIV infection. 862 8

We examined the ability of chemokine receptors and related G protein-coupled receptors to facilitate infection by primary, clinical HIV-1 isolates. CCR5, when expressed along with CD4, the HIV-1 receptor, allowed cell lines resistant to most primary HIV-1 isolates to be infected. CCR3 facilitated infection by a more restricted subset of primary viruses, and binding of the CCR3 ligand, eotaxin, inhibited infection by these isolates. Utilization of CCR3 and CCR5 on the target cell depended upon the sequence of the third variable (V3) region of the HIV-1 gp120 exterior envelope glycoprotein. The ability of various members of the chemokine receptor family to support the early stages of HIV-1 infection helps to explain viral tropism and beta-chemokine inhibition of primary HIV-1 isolates.
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PMID:The beta-chemokine receptors CCR3 and CCR5 facilitate infection by primary HIV-1 isolates. 867 19

Here, we show that the beta-chemokine receptor CKR-5 serves as a cofactor for M-tropic HIV viruses. Expression of CKR-5 with CD4 enables nonpermissive cells to form syncytia with cells expressing M-tropic, but not T-tropic, HIV-1 env proteins. Expression of CKR-5 and CD4 enables entry of a M-tropic, but not a T-tropic, virus strain. A dual-tropic primary HIV-1 isolate (89.6) utilizes both Fusin and CKR-5 as entry cofactors. Cells expressing the 89.6 env protein form syncytia with QT6 cells expressing CD4 and either Fusin or CKR-5. The beta-chemokine receptors CKR-3 and CKR-2b support HIV-1 89.6 env-mediated syncytia formation but do not support fusion by any of the T-tropic or M-tropic strains tested. Our results suggest that the T-tropic viruses characteristic of disease progression may evolve from purely M-tropic viruses prevalent early in virus infection through changes in the env protein that enable the virus to use multiple entry cofactors.
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PMID:A dual-tropic primary HIV-1 isolate that uses fusin and the beta-chemokine receptors CKR-5, CKR-3, and CKR-2b as fusion cofactors. 867 20

MIP-1 alpha is a secreted chemokine which can inhibit hematopoietic stem cells and modulate inflammatory responses. It is also an inhibitor of HIV replication in CD8+ T-cells. The expression of MIP-1 alpha is induced during cellular activation of CD4+ T-cells and monocytes. It is also expressed in transformed B-cells. We have previously identified a new transcription factor family (the MNP family) whose expression is crucial for the induction of MIP-1 alpha transcription during cellular activation and in transformed B cells. Monocytes and transformed B-cells normally express MNP-1 strongly and MNP-2 weakly, while T-cells strongly express only MNP-2. Recently, we reported that HIV-1 tat downregulates MIP-1 alpha expression in Jurkat T-cells. In this report we show induction of MNP-1 in Jurkat T-cells expressing HIV-1 tat. Expression of neither HTLV-1 tax in Jurkat T-cells nor EBV in B-cells had any effect on MNP-1 or MNP-2 expression, showing that the effect is specific for HIV-1 tat. We propose that HIV-1 tat may inhibit MIP-1 alpha expression by inducing MNP-1 expression in T-cells, probably by either competing with MNP-2 for binding to the MIP-1 alpha promoter or by sequestering it into inactive forms.
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PMID:HIV-1 tat induces the expression of a new hematopoietic cell-specific transcription factor and downregulates MIP-1 alpha gene expression in activated T-cells. 868 29

Chemokines are chemotactic cytokines that activate and direct the migration of leukocytes. There are two subfamilies, the CXC and the CC chemokines. We recently found that the CXC-chemokine stromal cell-derived factor-1 (SDF-1) is a highly efficacious lymphocyte chemoattractant. Chemokines act on responsive leukocyte subsets through G-protein-coupled seven-transmembrane receptors, which are also used by distinct strains of HIV-1 as cofactors for viral entry. Laboratory-adapted and some T-cell-line-tropic (T-tropic) primary viruses use the orphan chemokine receptor LESTR/fusin (also known as fusin), whereas macrophage-tropic primary HIV-1 isolates use CCR-5 and CCR-3 (refs 7-11), which are receptors for known CC chemokines. Testing of potential receptors demonstrated that SDF-1 signalled through, and hence 'adopted', the orphan receptor LESTR, which we therefore designate CXC-chemokine receptor-4 (CXCR-4). SDF-1 induced an increase in intracellular free Ca2+ and chemotaxis in CXCR-4-transfected cells. Because SDF-1 is a biological ligand for the HIV-1 entry cofactor LESTR, we tested whether it inhibited HIV-1. SDF-1 inhibited infection by T-tropic HIV-1 of HeLa-CD4 cells, CXCR-4 transfectants, and peripheral blood mononuclear cells (PBMCs), but did not affect CCR-5-mediated infection by macrophage-tropic (M-tropic) and dual-tropic primary HIV-1.
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PMID:The lymphocyte chemoattractant SDF-1 is a ligand for LESTR/fusin and blocks HIV-1 entry. 875 80

A putative chemokine receptor that we previously cloned and termed LESTR has recently been shown to function as a co-receptor (termed fusin) for lymphocyte-tropic HIV-1 strains. Cells expressing CD4 became permissive to infection with T-cell-line-adapted HIV-1 strains of the syncytium-inducing phenotype after transfection with LESTR/fusin complementary DNA. We report here the indentification of a human chemokine of the CXC type, stromal cell-derived factor 1 (SDF-1), as the natural ligand for LESTR/fusin, and we propose the term CXCR-4 for this receptor, in keeping with the new chemokine-receptor nomenclature. SDF-1 activates Chinese hamster ovary (CHO) cells transfected with CXCR-4 cDNA as well as blood leukocytes and lymphocytes. In cell lines expressing CXCR-4 and CD4, and in blood lymphocytes, SDF-1 is a powerful inhibitor of infection by lymphocyte-tropic HIV-1 strains, whereas the CC chemokines RANTES, MIP-1 alpha and MIP-1 beta, which were shown previously to prevent infection with primary, monocyte-tropic viruses, are inactive. In combination with CC chemokines, which block the infection with monocyte/macrophage-tropic viruses, SDF-1 could help to decrease virus load and prevent the emergence of the syncytium-inducing viruses which are characteristic of the late stages of AIDS.
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PMID:The CXC chemokine SDF-1 is the ligand for LESTR/fusin and prevents infection by T-cell-line-adapted HIV-1. 875 81

MIP-1 alpha is a secreted chemokine which can inhibit hematopoietic stem cells and modulate inflammatory responses. It is also an inhibitor of HIV replication in CD8+ T-cells, MIP-1 alpha is expressed in transformed B cells and can also be induced during cellular activation of CD4+ T-cells and monocytes. We have previously identified a new transcription factor family (the MNP family) whose expression is crucial for the induction of MIP-1 alpha transcription during cellular activation. Monocytes and transformed B-cells normally express MNP-1 strongly and MNP-2 weakly, while T-cells strongly express only MNP-2. In this communication we show evidence identifying a new member of the MNP transcription family, MNP-3, in PMA differentiated HL60 cells.
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PMID:Identification of a new member of the MNP transcription factor family in differentiated HL60 cells. 880 61

CD4 is widely known as the HIV receptor, but is insufficient to allow viral infection. Recently, members of the family of chemokine receptors have been identified as the missing co-receptors, which act with CD4 to allow the virus to enter cells. These discoveries open up the possibilities of novel therapeutic strategies to combat HIV infection and AIDS.
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PMID:Chemokine receptors - the new frontier for AIDS research. 880 92

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


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