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 serum levels of the beta-chemokine RANTES and, albeit less, MIP-1 beta were found to be increased in 37 HIV-1 infected compared to seronegative individuals. In contrast the serum levels of IL-16 were only sporadically elevated in seropositives as well as in seronegatives. Concomitantly, the RANTES gene expression increased about tenfold in seropositives, whereas the MIP-1 beta and IL-16 mRNA levels were not elevated. No correlation between the increase of the MIP-1 beta and RANTES serum concentrations and the plasma virus load, the number of the peripheral CD4+ T cells or the therapy status of the patients was found. However, the increased proportion of activated CD8+CD38+ T cells in the peripheral blood of all seropositives paralleled the increased RANTES serum levels detected indicating that immune activation in HIV-1-infected individuals may contribute to increased RANTES serum levels.
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PMID:Increased serum and mRNA levels of RANTES associated with elevated levels of activated CD8+CD38+ T cells in HIV-1 infected individuals. 961 28

Chemokines (chemotactic cytokines) are a family of immune system proteins, several of which have been shown to block human immunodeficiency virus (HIV) infection in various cell types. While the solved structures of most chemokines reveal protein dimers, evidence has accumulated for the biological activity of individual chemokine monomers, and a debate has arisen regarding the biological role of the chemokine dimer. Concurrent with this debate, several N-terminal truncations and modifications in the CC subfamily of chemokines have been shown to have functional significance, in many cases antagonizing their respective receptors and in some cases retaining the ability to block HIV entry to the cell. As the dimer interface of CC chemokines is located at their N-terminus, a structural study of N-terminally truncated chemokines will address the effect that this type of mutation has on the dimer-monomer equilibrium. We have studied the structural consequences of N-terminal truncation in macrophage inflammatory protein 1 beta (MIP-1 beta), a CC chemokine that has been shown to block HIV infection. Examination of nuclear magnetic resonance (NMR) spectra of a series of N-terminally truncated MIP-1 beta variants reveals that these proteins possess a range of ability to dimerize. A mutant beginning at amino acid Asp6 [termed MIP(6)] has near wild-type dimer properties, while further truncation results in weakened dimer affinity. The mutant MIP(9) (beginning with amino acid Thr9) has been found to exist solely as a folded monomer. Relaxation measurements yield a rotational correlation time of 8.6 +/- 0.1 ns for wild-type MIP-1 beta and 4.5 +/- 0.1 ns for the MIP(9) mutant, consistent with a wild-type dimer and a fully monomeric MIP(9) variant. The presence of physiological salt concentration drastically changes the monomer-dimer equilibrium for both wild-type and most mutant proteins, heavily favoring the dimeric form of the protein. These results have implications for structure-function analysis of existing chemokine mutants as well as for the larger debate regarding the biological existence and activity of the chemokine dimer.
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PMID:Effect of N-terminal truncation and solution conditions on chemokine dimer stability: nuclear magnetic resonance structural analysis of macrophage inflammatory protein 1 beta mutants. 964 15

Although evidence for human immunodeficiency virus 1 (HIV-1) presence in the central nervous system (CNS) of infected patients is well established, the intensity of viral replication within the brain is not usually known. In vitro, human embryonic microglial cells internalized HIV-1 through a CD4-dependent pathway but were not permissive to viral replication. We observed that HIV replication was induced when CNS cell cultures were stimulated for 14 days by a combination of proinflammatory cytokines including IFNgamma, IL1beta, and TNFalpha. After long-term cytokine stimulation, morphologically differentiated glial cells appeared, in which HIV-1 tat antigen was detected after infection. Thus, variations in the stage of maturation/activation of CNS cells under inflammatory conditions probably play a major role in facilitating massive production of HIV-1. We then studied the effect of prolonged cytokine stimulation on the secretion of inflammatory mediators by glial cells. An early increased secretion of prostaglandin F2alpha and chemokines (RANTES>>MIP-1alpha>>MIP-1beta) was observed, due to both microglia and astrocytes. In contrast to persistent PGF2alpha production, an extinction of RANTES and MIP-1beta but not of MIP-1alpha secretion occurred during the 14 days of stimulation and was inversely correlated with the ability of glial cells to replicate HIV-1. The study of the secretory factors produced in response to a persistent inflammation could provide a better understanding of the modulation of HIV replication in glial cells.
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PMID:Induction of human immunodeficiency virus type 1 replication in human glial cells after proinflammatory cytokines stimulation: effect of IFNgamma, IL1beta, and TNFalpha on differentiation and chemokine production in glial cells. 967 61

In this study, we examined the difference in susceptibility to anti-HIV activity of the CC-chemokines (RANTES, MIP-1 alpha and MIP-1 beta) among HIV-1 isolates and analysed its relation with phenotype (syncytium inducibility) and V3 domain of gp120 of the HIV-1 isolates. Of 11 cases tested in endogenous assay, at a concentration of 200 ng/ml, RANTES, MIP-1 alpha, and MIP-1 beta showed more than 80% suppression of HIV-1 replication in 10, 8, and 7 cases, respectively. HIV-1 isolates sensitive to more than one CC-chemokine showed non-syncytium-inducing phenotype, whereas HIV-1 isolates resistant to all of the 3 CC-chemokines showed syncytium-inducing phenotype. HIV-1 isolates resistant to all of the 3 CC-chemokines contained more positively charged amino acid residues in the V3 domain of the gp120. These results indicated that utilization of the CC-chemokine receptors as co-receptors for virus entry could vary among HIV-1 isolates.
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PMID:Difference in susceptibility to CC-chemokines among HIV-1 isolates. 970 96

The Duffy Antigen Receptor for Chemokines (DARC) belongs to a family of erythrocyte chemokine receptors that bind C-X-C and C-C chemokines such as interleukin 8 (IL-8), monocyte chemoattractant protein 1 (MCP-1) and regulated-on-activation, normal T cell-expressed and -secreted (RANTES), but not macrophage inflammatory protein 1 alpha (MIP-1 alpha) or MIP-1 beta. DARC has also been identified to a receptor for malaria parasites Plasmodium vivax and Plasmodium knowlesi. In the present study, we show that HIV-1 binds to RBCs from Caucasian individuals via DARC making RBCs able to transmit HIV to peripheral blood mononuclear cells (PBMCs). Furthermore, binding of HIV-1 particles to RBCs is inhibited by treating these cells with recombinant RANTES, but not with recombinant MIP-1 alpha prior to their incubation with HIV-1. This finding suggests that RBCs may function as a reservoir for HIV-1 or as a receptor for the entry of HIV-1 into CD4-cell subsets as well as neurons or endothelial cells.
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PMID:Binding of HIV-1 to RBCs involves the Duffy antigen receptors for chemokines (DARC). 992 12

CD8+ cell-secreted CC-chemokines, MIP-1alpha, and MIP-beta have recently been identified as factors which suppress HIV. In this study we co-inoculated MIP-1alpha expression plasmid with a DNA vaccine constructed from HIV-1 pCMV160IIIB and pcREV, and evaluated the effect of the adjuvant on HIV-specific immune responses following intramuscular and intranasal immunization. The levels of both cytotoxic T lymphocyte (CTL) activity and DTH showed that HIV-specific cell-mediated immunity (CMI) was significantly enhanced by co-inoculation of the MIP-1alpha expression plasmid with the DNA vaccine compared with inoculation of the DNA vaccine alone. The HIV-specific serum IgG1/IgG2a ratio was significantly lowered when the plasmid was co-inoculated in both intramuscular and intranasal routes, suggesting a strong elicitation of the T helper (Th) 1-type response. When the MIP-1alpha expression plasmid was inoculated intramuscularly with the DNA vaccine, an infiltration of mononuclear cells was observed at the injection site. After intranasal administration, the level of mucosal secretory IgA antibody was markedly enhanced. These findings demonstrate that MIP-1alpha expression plasmid inoculated together with DNA vaccine acts as a strong adjuvant for eliciting Th1-derived immunity.
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PMID:Macrophage inflammatory protein-1alpha (MIP-1alpha) expression plasmid enhances DNA vaccine-induced immune response against HIV-1. 993 62

Chemokine receptors and related seven-transmembrane-segment (7TMS) receptors serve as coreceptors for entry of human and simian immunodeficiency viruses (HIV-1, HIV-2, and SIV) into target cells. Each of these otherwise diverse coreceptors contains an N-terminal region that is acidic and tyrosine rich. Here, we show that the chemokine receptor CCR5, a principal HIV-1 coreceptor, is posttranslationally modified by O-linked glycosylation and by sulfation of its N-terminal tyrosines. Sulfated tyrosines contribute to the binding of CCR5 to MIP-1 alpha, MIP-1 beta, and HIV-1 gp120/CD4 complexes and to the ability of HIV-1 to enter cells expressing CCR5 and CD4. CXCR4, another important HIV-1 coreceptor, is also sulfated. Tyrosine sulfation may contribute to the natural function of many 7TMS receptors and may be a modification common to primate immunodeficiency virus coreceptors.
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PMID:Tyrosine sulfation of the amino terminus of CCR5 facilitates HIV-1 entry. 1008 82

Chemokines play diverse roles in inflammatory and non-inflammatory situations via activation of heptahelical G-protein-coupled receptors. Also, many chemokine receptors can act as cofactors for cellular entry of human immunodeficiency virus (HIV) in vitro. CCR5, a receptor for chemokines MIP-1alpha (LD78alpha), MIP-1beta, RANTES, and MCP2, is of particular importance in vivo as polymorphisms in this gene affect HIV infection and rate of progression to AIDS. Moreover, the CCR5 ligands can prevent HIV entry through this receptor and likely contribute to the control of HIV infection. Here we show that a non-allelic isoform of human MIP-1alpha (LD78alpha), termed LD78beta or MIP-1alphaP, has enhanced receptor binding affinities to CCR5 (approximately 6-fold) and the promiscuous beta-chemokine receptor, D6 (approximately 15-20-fold). We demonstrate that a proline residue at position 2 of MIP-1alphaP is responsible for this enhanced activity. Moreover, MIP-1alphaP is by far the most potent natural CCR5 agonist described to date, and importantly, displays markedly higher HIV1 suppressive activity than all other human MIP-1alpha isoforms examined. In addition, while RANTES has been described as the most potent inhibitor of CCR5-mediated HIV entry, MIP-1alphaP was as potent as, if not more potent than, RANTES in HIV-1 suppressive assays. This property suggests that MIP-1alphaP may be of importance in controlling viral spread in HIV-infected individuals.
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PMID:LD78beta, a non-allelic variant of human MIP-1alpha (LD78alpha), has enhanced receptor interactions and potent HIV suppressive activity. 1036 78

Vgamma9Vdelta2 T lymphocytes are broadly reactive against various intracellular pathogens and display both lytic and proliferative responses to human immunodeficiency virus (HIV)-infected cells. HIV infection of peripheral blood mononuclear cell cultures led to absolute increases in Vgamma9Vdelta2 T cells accompanied by decreased p24 levels. Strong gammadelta T cell activation with nonpeptidic mycobacterial phosphoantigens (TUBAg1 extract or synthetic isopentenyl pyrophosphate) resulted in potent inhibition of HIV replication through soluble released factors. Subsequent analyses showed that phosphoantigen-activated gammadelta T cells produced substantial amounts of beta-chemokines (macrophage inflammatory protein [MIP]-1alpha, MIP-1beta, and regulated-on-activation, normal T-cell-expressed and -secreted beta-chemokine [RANTES]), which represent the natural ligand for the CCR5 HIV coreceptor. Accordingly, anti-beta-chemokine antibodies neutralized the inhibition of monocytotropic HIV strains by gammadelta T cell-released factors. Moreover, a T-tropic HIV strain using the CXCR4 coreceptor for virus entry was potently inhibited. Together, these data reveal that phosphoantigen-activated gammadelta T cells are an important source of CC chemokines and may suppress HIV replication through cell-released antiviral factors.
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PMID:Phosphoantigen-reactive Vgamma9Vdelta2 T lymphocytes suppress in vitro human immunodeficiency virus type 1 replication by cell-released antiviral factors including CC chemokines. 1043 80

Two syndromes affecting cognitive and motor function in the setting of AIDS have been described as HIV encephalopathy (HIVE) and progressive multifocal leukoencephalopathy (PML). HIVE is characterized by the presence of microglial nodules with accompanying astrocytosis. PML is a fatal demyelinating disease of the white matter induced by the human papovavirus JCV which causes cytolytic destruction of glial cells. In addition to the effect of HIV-1 induced immune suppression, HIV may act directly as a co-factor for stimulation of JCV replication in AIDS patients, in part due to Tat-induced activation of JCV gene transcription. Since Tat has been implicated in CNS pathogenesis, we examined its localization in CNS specimens from HIV infected patients with HIVE and PML as well as controls. Based on the observation of CC chemokine induction in monocytes by Tat, we also examined the cellular localization of the CC chemokine Macrophage Inflammatory Protein-1alpha (MIP-1alpha) and its cognate receptor CCR-5 in these samples. In HIVE, Tat was primarily localized in astrocytes and microglia, within the nodular lesions. In PML, a marked increase in the number of Tat positive astrocytes was observed. In both HIVE and PML, prominent expression of MIP-1alpha and CCR-5 was found within areas containing histopathological lesions. CCR-5 positivity of microglia was localized primarily to nodular lesions in HIVE. In PML, increased numbers of cells with monocyte/microglial morphology were observed relative to HIVE. The increased MIP-1 alpha positivity, and potentially other chemokines, may contribute to the pathogenesis of PML in the setting of HIV infection. Tat may play an important role in the pathogenesis of both HIV associated CNS disease states, acting indirectly through cytokine and chemokine dysregulation.
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PMID:Role of HIV-1 Tat and CC chemokine MIP-1alpha in the pathogenesis of HIV associated central nervous system disorders. 1060 9


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