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

Some individuals remain uninfected with human immunodeficiency virus type-1 (HIV-1) despite multiple high-risk sexual exposures. We studied a cohort of 25 subjects with histories of multiple high-risk sexual exposures to HIV-1 and found that their CD8+ lymphocytes had greater anti-HIV-1 activity than did CD8+ lymphocytes from nonexposed controls. Further studies indicated that their purified CD4+ lymphocytes were less susceptible to infection with multiple primary isolates of HIV-1 than were CD4+ lymphocytes from the nonexposed controls. This relative resistance to HIV-1 infection did not extend to T-cell line-adapted strains, was restricted by the envelope glycoprotein, was not explained by the cell surface density of CD4 molecules, but was associated with the activity of the C-C chemokines RANTES, MIP-1alpha, and MIP-1beta. This relative resistance of CD4+ lymphocytes may contribute to protection from HIV-1 in multiply exposed persons.
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PMID:Relative resistance to HIV-1 infection of CD4 lymphocytes from persons who remain uninfected despite multiple high-risk sexual exposure. 859 50

Entry of HIV-1 into target cells requires cell-surface CD4 and additional host cell cofactors. A cofactor required for infection with virus adapted for growth in transformed T-cell lines was recently identified and named fusin. However, fusin does not promote entry of macrophage-tropic viruses, which are believed to be the key pathogenic strains in vivo. The principal cofactor for entry mediated by the envelope glycoproteins of primary macrophage-tropic strains of HIV-1 is CC-CKR-5, a receptor for the beta-chemokines RANTES, MIP-1alpha and MIP-1beta.
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PMID:Identification of a major co-receptor for primary isolates of HIV-1. 864 6

The beta-chemokines MIP-1alpha, MIP-1beta and RANTES inhibit infection of CD4+ T cells by primary, non-syncytium-inducing (NSI) HIV-1 strains at the virus entry stage, and also block env-mediated cell-cell membrane fusion. CD4+ T cells from some HIV-1-exposed uninfected individuals cannot fuse with NSI HIV-1 strains and secrete high levels of beta-chemokines. Expression of the beta-chemokine receptor CC-CKR-5 in CD4+, non-permissive human and non-human cells renders them susceptible to infection by NSI strains, and allows env-mediated membrane fusion. CC-CKR-5 is a second receptor for NSI primary viruses.
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PMID:HIV-1 entry into CD4+ cells is mediated by the chemokine receptor CC-CKR-5. 864 6

Human immunodeficiency virus-type 1 (HIV-1) entry requires fusion cofactors on the CD4+ target cell. Fusin, a heterotrimeric GTP-binding protein (G protein)-coupled receptor, serves as a cofactor for T cell line-tropic isolates. The chemokines RANTES, MIP-1alpha, and MIP-1beta, which suppress infection by macrophage-tropic isolates, selectively inhibited cell fusion mediated by the corresponding envelope glycoproteins (Envs). Recombinant CC CKR5, a G protein-coupled receptor for these chemokines, rendered CD4-expressing nonhuman cells fusion-competent preferentially with macrophage-tropic Envs. CC CKR5 messenger RNA was detected selectively in cell types susceptible to macrophage-tropic isolates. CC CKR5 is thus a fusion cofactor for macrophage-tropic HIV-1 strains.
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PMID:CC CKR5: a RANTES, MIP-1alpha, MIP-1beta receptor as a fusion cofactor for macrophage-tropic HIV-1. 865 71

For efficient entry into target cells, primary macrophage-tropic and laboratory-adapted human immunodeficiency viruses type 1 (HIV-1) require particular chemokine receptors, CCR-5 and CXCR-4, respectively, as well as the primary receptor CD4 (refs 1-6). Here we show that a complex of gp120, the exterior envelope glycoprotein, of macrophage-tropic primary HIV-1 and soluble CD4 interacts specifically with CCR-5 and inhibits the binding of the natural CCR-5 ligands, macrophage inflammatory protein (MIP)-1alpha and MIP-1beta (refs 7, 8). The apparent affinity of the interaction between gp120 and CCR-5 was dramatically lower in the absence of soluble CD4. Additionally, in the absence of gp120, an interaction between a two-domain CD4 fragment and CCR-5 was observed. A gp120 fragment retaining the CD4-binding site and overlapping epitopes was able to interact with CCR-5 only if the V3 loop, which can specify HIV-1 tropism and chemokine receptor choice, was also present on the molecule. Neutralizing antibodies directed against either CD4-induced or V3 epitopes on gp120 blocked the interaction of gp12O-CD4 complexes with CCR-5. These results suggest that HIV-1 attachment to CD4 creates a high-affinity binding site for CCR-5, leading to membrane fusion and virus entry.
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PMID:CD4-induced interaction of primary HIV-1 gp120 glycoproteins with the chemokine receptor CCR-5. 890 82

Several members of the chemokine receptor family are used together with CD4 for HIV-1 entry into target cells. T cell line-tropic (T-tropic) HIV-1 viruses use the chemokine receptor CXCR4 as a co-receptor, whereas macrophage-tropic (M-tropic) primary viruses use CCR5 (refs 2-6). Individuals with defective CCR5 alleles exhibit resistance to HIV-1 infection, suggesting that CCR5 has an important role in vivo in HIV-1 replication. A subset of primary viruses can use CCR3 as well as CCR5 as a co-receptor, but the in vivo contribution of CCR3 to HIV-1 infection and pathogenesis is unknown. HIV-1 infects the central nervous system (CNS) and causes the dementia associated with AIDS. Here we report that the major target cells for HIV-1 infection in the CNS, the microglia, express both CCR3 and CCR5. The CCR3 ligand, eotaxin, and an anti-CCR3 antibody inhibited HIV-1 infection of microglia, as did MIP-1beta, which is a CCR5 ligand. Our results suggest that both CCR3 and CCR5 promote efficient infection of the CNS by HIV-1.
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PMID:CCR3 and CCR5 are co-receptors for HIV-1 infection of microglia. 902 64

Entry of human immunodeficiency virus type 1 (HIV-1) requires CD4 and one of a family of related seven-transmembrane-domain coreceptors. Macrophage-tropic HIV-1 isolates are generally specific for CCR5, a receptor for the CC chemokines RANTES, MIP-1alpha, and MIP-1beta, while T-cell line-tropic viruses tend to use CXCR4 (also known as fusin, LESTR, or HUMSTR). Like HIV-1, simian immunodeficiency virus (SIV) requires CD4 on the target cell surface; however, whether it also requires a coreceptor is not known. We report here that several genetically divergent SIV isolates, including SIVmac, SIVsmSL92a, SIVsmLib-1, and SIVcpzGAB, can use human and rhesus CCR5 for entry. CXCR4 did not facilitate entry of any of the simian viruses tested, nor did any of the other known chemokine receptors. Moreover, SIVmac251 that had been extensively passaged in a human transformed T-cell line retained its use of CCR5. Rhesus and human CCR5 differed at only eight amino acid residues, four of which were in regions of the receptor that could be exposed, two in the amino-terminal extracellular region and two in the second extracellular loop. The human coreceptor was as active as the simian for SIV entry. In addition, HIV-1 was able to use the rhesus homologs of the human coreceptors, CCR5 and CXCR4. The SIV strains tested were specific for CCR5 regardless of whether they were able to replicate in transformed T-cell lines or macrophages and whether they were phenotypically syncytium inducing or noninducing in MT-2 cells. However, SIV replication was not restricted to cells expressing CCR5. SIV strains replicated efficiently in the human transformed lymphoid cell line CEMx174, which does not express detectable amounts of transcripts of CCR5. SIV also replicated in human peripheral blood mononuclear cells that were genetically deficient in CCR5. These findings indicated that, in addition to CCR5, SIV can use one or more unknown coreceptors that are expressed on human PBMCs and CEMx174 cells.
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PMID:Genetically divergent strains of simian immunodeficiency virus use CCR5 as a coreceptor for entry. 906 Jun 23

Although CD8+ lymphocytes in human immunodeficiency virus type 1 (HIV-1)-infected individuals have been demonstrated to suppress viral replication, the mechanisms of inhibition have not been defined precisely. A large body of evidence indicates that these cells act via soluble inhibitory factors, but the potential role of HLA class I-restricted cytolysis has remained controversial. Here we demonstrate that HIV-1-specific cytotoxic T lymphocytes (CTL) mediate antiviral suppression by both cytolytic and noncytolytic mechanisms. The predominant mechanism requires direct contact of CTL with the infected cells, is HLA class I restricted, and can achieve complete elimination of detectable virus in infected cell cultures. Inhibition occurs even at high multiplicities of infection or at ratios of CTL to CD4 cells as low as 1:1,000. The other mechanism is mediated by soluble inhibitory factors which are triggered in an antigen-specific and HLA-restricted fashion but then act without HLA restriction. These include MIP-1alpha, MIP-1beta, and RANTES, as well as a distinct factor(s) capable of inhibiting HIV-1 strains insensitive to these chemokines. These data indicate that HIV-1-specific CTL are potent mediators of HIV-1 suppression at cell ratios existing in vivo and demonstrate an antigen-specific trigger for CD8+ cell-derived soluble inhibitory factors. These results suggest that CTL play an important role in the observed antiviral activity of CD8+ cells from infected individuals.
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PMID:Suppression of human immunodeficiency virus type 1 replication by CD8+ cells: evidence for HLA class I-restricted triggering of cytolytic and noncytolytic mechanisms. 906 Jun 75

Ligation of CCR5 by the CC chemokines RANTES, MIP-1alpha or MIP-1beta, and of CXCR4 by the CXC chemokine SDF-1alpha, profoundly inhibits the replication of HIV strains that use these coreceptors for entry into CD4(+) T lymphocytes. The mechanism of entry inhibition is not known. We found a rapid and extensive downregulation of CXCR4 by SDF-1alpha and of CCR5 by RANTES or the antagonist RANTES(9-68). Confocal laser scanning microscopy showed that CCR5 and CXCR4, after binding to their ligands, are internalized into vesicles that qualify as early endosomes as indicated by colocalization with transferrin receptors. Internalization was not affected by treatment with Bordetella pertussis toxin, showing that it is independent of signaling via Gi-proteins. Removal of SDF-1alpha led to rapid, but incomplete surface reexpression of CXCR4, a process that was not inhibited by cycloheximide, suggesting that the coreceptor is recycling from the internalization pool. Deletion of the COOH-terminal, cytoplasmic domain of CXCR4 did not affect HIV entry, but prevented SDF-1alpha-induced receptor downregulation and decreased the potency of SDF-1alpha as inhibitor of HIV replication. Our results indicate that the ability of the coreceptor to internalize is not required for HIV entry, but contributes to the HIV suppressive effect of CXC and CC chemokines.
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PMID:HIV coreceptor downregulation as antiviral principle: SDF-1alpha-dependent internalization of the chemokine receptor CXCR4 contributes to inhibition of HIV replication. 920 8

Soluble factors derived from human CD8+ T-lymphocytes inhibit HIV-1 replication by suppressing transcription from the viral long terminal repeat (LTR), an effect shown to be mediated in part by an NFAT-1 enhancer sequence. We show here that the CD8+ derived beta-chemokines, RANTES, MIP1-alpha, and MIP-1beta, known suppressors of HIV-1 replication in human peripheral blood mononuclear cells, can suppress transcription from the HIV-1 LTR in transient transfection assays in cells of the Jurkat (acute T leukemia) line. Surprisingly, the suppression mediated by these beta-chemokines persisted in the absence of an intact NFAT-1 element, suggesting that there are at least two classes of HIV-1 suppressor factors--NFAT-1-dependent and NFAT-1-independent factors--produced by CD8+ T-lymphocytes.
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PMID:Suppression of HIV-1 transcription by beta-chemokines RANTES, MIP1-alpha, and MIP-1beta is not mediated by the NFAT-1 enhancer element. 923 50


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