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Envelope surface glycoprotein gp120
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env
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The CCR5 chemokine receptor is required for the entry of macrophage-tropic HIV-1 into target cells; the HIV-1 gp120-CD4 complex binds CCR5, which inhibits the binding of the natural CCR5 ligands macrophage inflammatory protein (MIP)-1alpha and MIP-1beta |
PubMed
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env
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The specific amino acids 298-329 in the V3 loop of HIV-1 gp120 that determine cellular tropism also regulate chemokine coreceptor (CCR5 or CXCR4) preference for cell entry by the virus |
PubMed
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env
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HIV-1 Env (gp120) V3 loop binds to CXCR4 and CCR5 through in silico analysis |
PubMed
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env
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HIV-1 JR-CSF Env binds CCR5 but is abrogated by the mutation K421D |
PubMed
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env
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HIV-1 JR-CSF Env mutant S142N binds CCR5 with better affinity |
PubMed
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env
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HIV-1 gp120 binds to CCR5 with decreased affinity when an alanine insertion within the GPG (G310_P311insA) of the gp120 VL3 (resulting from Maraviroc pressure) is present; molecular simulations indicate weakened interaction with CCR5 extracellular loop 2 |
PubMed
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env
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HIV-1 Env gp120 (JRFL) interacts with the extracellular loop 1 of CCR5 and these interactions are functionally critical; adaptation to murine extracellular loop 1 requires multiple mutations in the crown of gp120s V3 loop |
PubMed
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env
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HIV-1 gp120 D197 and T/V200 increase fusion and infection of cells expressing low CD4 by enhancing gp120 binding to CCR5 |
PubMed
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env
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Two-dimensional saturation transfer difference NMR spectroscopy and dynamic filtering studies reveal involvement of residues Y187, F189, W190 and F193 of the second extracellular loop of CCR5 in the interaction with HIV-1 gp120 |
PubMed
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env
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Antibodies to specific epitopes of HIV-1 gp120 block the interaction of CCR5 with the gp120/CD4 complex, suggesting that a CD4-mediated conformational change in gp120 is required for subsequent binding to CCR5 |
PubMed
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env
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The amino-terminal residues (amino acids 1-25) and three extracellular loops (amino acids 88-102, 168-194, 261-277) of the CCR5 coreceptor are highly involved in its binding to gp120 from macrophage-tropic HIV-1 strains and in CCR5-mediated HIV-1 entry |
PubMed
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env
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Anti-CCR5 monoclonal antibodies efficiently prevent HIV-1 infection by inducing receptor dimerization, but not by interfering with HIV-1 gp120 binding to CCR5 |
PubMed
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env
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The binding of HIV-1 gp120 to CCR5 and entry of macrophage-tropic HIV-1 isolates into cells is blocked by CCR5 antagonists or the chemokine RANTES, which interacts with CCR5 |
PubMed
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env
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The coreceptor-binding site in HIV-1 gp120 is centered around an anti-parallel beta-sheet structure 'bridging sheet domain'; mutations in and adjacent to this domain have greater impact on CXCR4-mediated fusion than on CCR5-mediated fusion |
PubMed
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env
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Interaction of HIV-1 gp120 with CCR5 upregulates IL-6 expression in primary human monocyte-derived dendritic cells |
PubMed
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env
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CCR5 expression inhibits HIV-1 gp120-induced LIMK1 activation and cofilin phosphorylation in CD4/CXCR4 expressing 293T cells |
PubMed
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env
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CCR5 expression inhibits HIV-1 gp120 binding to CD4/CXCR4 complexes in 293T cells |
PubMed
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env
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CCR5 expression inhibits HIV-1 gp120-mediated early actin rearrangement in CD4/CXCR4 expressing 293T cells |
PubMed
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env
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HIV-1 gp120-enhanced CD4/CXCR4 conformation changes are regulated by CCR5 expression in 293T cells |
PubMed
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env
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SMS2, but not SMS1, is involved in enhancement of HIV-1 gp120/gp41-mediated membrane fusion through CD4 receptor and CCR5/CXCR4 coreceptors |
PubMed
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env
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HIV-1 gp120 mutant K421D exhibits inefficient entry at low levels of CCR5, while K421D responses dramatically to the entry at high levels of CCR5 |
PubMed
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env
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Negatively charged Asp/Glu at position 322 in the V3 of gp120 and positively charged Arg at position 440 in the C4 of gp120 occur more frequently in CCR5-using strains |
PubMed
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env
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V1, V2, and V3 domains and N-linked glycosylation sites of HIV-1 gp120 confer coreceptor tropism; loss of an N-linked glycosylation site within V3 has a major influence on the virus switching from CCR5 to CXCR4 tropism in a V3 charge-dependent manner |
PubMed
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env
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A single sulfotyrosine residue 14 in CCR5 is recognized by HIV-1 gp120 |
PubMed
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env
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In addition to the V3 loop of HIV-1 gp120, some conserved amino acid residues (117-123, 207, 419-422, and 438-441) are also involved in CCR5 chemokine receptor binding |
PubMed
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env
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HIV-1 gp120 mutations S298N, F313L, and N403S result in weakening gp120's grip on gp41 rather than altering gp120 binding to specific CCR5 sites |
PubMed
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env
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Peptides from a library inhibit HIV-1 replication in vitro through blocking of HIV-1 gp120 interaction with the co-receptor CCR5 |
PubMed
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env
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Analysis of the distribution of V3 loop's net charge and flexibility in HIV-1 gp120 shows its selection more positive toward CXCR4 than CCR5 |
PubMed
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env
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Interaction of the trimeric gp120 with CCR5 coreceptor triggers dendritic cells (DCs) to migrate between intestinal epithelial cells to sample virions and transfer infection to target cells |
PubMed
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env
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Gelsolin overexpression impairs HIV-1 gp120-induced cortical F-actin reorganization and capping and gp120-mediated CD4-CCR5 and CD4-CXCR4 redistribution in permissive lymphocytes |
PubMed
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env
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HIV-1 gp120 binds and signals through CD4, which leads to T cell activation with upregulation of the CXCR5, PD-1, Fas, and FasL expression |
PubMed
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env
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HIV-1 gp120-induced dephosphorylation of KV2.1 and re-localization of KV2.1 on the soma and proximal dendrites results in disruption of the clustered KV2.1 via activation of CCR5/CXCR4 co-receptors or SDF-1 alpha treatment |
PubMed
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env
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The V3 loop of brain-derived HIV-1 Env gp120 proteins significantly reduces the contact with N-terminal interface (Tyr10, Asn13, and Tyr14) of CCR5 as compared to lymph-node-derived gp120 proteins |
PubMed
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env
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HIV-1 gp120/41 Envelope proteins form a complex with integrin alpha4beta7 and chemokine receptor CCR5 on the CD4-negative gamma-delta T cell membrane, which leads to activation of the p38-caspase pathway and induces the death of gamma-delta cells |
PubMed
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env
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Antibodies to specific epitopes of the CCR5 or CXCR4 chemokine receptors inhibit the entry of M-tropic, T-tropic, or dual-tropic HIV-1 into target cells by blocking the interaction of the receptors with the HIV-1 gp120/CD4 complex |
PubMed
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env
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Binding of HIV-1 gp120 to CCR5 causes NHERF1-mediated activation of RhoA |
PubMed
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env
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Stimulation of cells with HIV-1 gp120 induces the interaction of endogenous CCR5 with NHERF1, which enhances CCR5 internalization |
PubMed
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env
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HIV-1 R5-tropic Env-mediated apoptosis of bystander cells is dependent on both CCR5 expression levels and fusogenic activity of the Env glycoprotein through the mechanism of apoptosis involved caspase-3 activation and mitochondrial depolarization |
PubMed
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env
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NMR studies find the strong interaction of sulfated (CCR5)Tyr14 with (gp120)Arg440 |
PubMed
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env
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The C-terminal region of CCR5 second extracellular loop (ECL2) comprising Cys178-Lys191 is sufficient for inhibition of HIV-1 entry by R5 and X4 strains. Peptides derived from ECL2 form a complex with HIV-1 gp120 |
PubMed
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env
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Deaminases APOBEC3F- and APOBEC3G-mediated G-to-A mutations in the V3 region of HIV-1 gp120 lead to the co-receptor switch from R5 to X4 strains |
PubMed
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env
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Genistein, tyrosine kinase inhibitor, inhibits cell fusion between macrophages and HIV-1 Env expressing cells. Genistein treatment does not change CD4 or CCR5 surface expression and has no effect on gp120-CD4-CCR5 complex formation |
PubMed
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env
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HIV-1 gp120-induced PI3-kinase activity and calcium mobilization are inhibited by pertussis toxin and blocking antibodies directed against CCR5 and CXCR4, suggesting that this signaling is mediated through these chemokine receptors |
PubMed
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env
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Sulfation of CCR5 by tyrosylprotein sulfotranferase-2 is crucial for mediating interaction with HIV-1 gp120. The pattern and the rate of sulfation for CCR5 depend on the number of amino acids N-terminal of Tyr-3 |
PubMed
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env
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HIV-1 gp120-induced Ca(2+) fluxing is CD4 dependent and coreceptor specific, and is mediated by the CCR5 and CXCR4 coreceptors |
PubMed
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env
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N362, a potential N-linked glycosylation site immediately N-terminal to CD4-binding site residues in the C3 region of gp120, contributes to fusogenicity of R5 Envs in a strain dependent manner |
PubMed
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env
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Individual gp120-CD4 bonds undergo rapid destabilization and this destabilization is significantly enhanced by the coreceptor CCR5, not by CXCR4 |
PubMed
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env
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CCR5 activation by gp120 triggers the assembly of endogenous Lyn, PI3K, and Pyk2 and is associated with PI3K and Pyk2 translocation from the cytoplasm to the membrane where they colocalized with Lyn |
PubMed
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env
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HIV-1 gp120 induces IL-1beta release from macrophages in a time- and concentration-dependent manner through binding to the chemokine receptor CCR5 and coupling to G(i)alpha protein |
PubMed
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env
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Introduction of G312V and A204E to multiple subtype A Envs and substitution of G312 and A204 with other residues increase CCR5-dependent entry into pig-tailed macaque lymphocytes |
PubMed
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env
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Soluble HIV-1 gp120 protein induces CCR5 downregulation on activated CD4+ T-cells in HIV-infected individuals |
PubMed
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env
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HIV-1 gp120 hydrogen bond interactions among transmembrane residues Y108, E283, and Y251, are crucial for HIV-1-gp120/sCD4 complex binding and HIV-1 fusion. HIV-1 gp120 binding to CCR5 disrupts these interhelix hydrogen bond interactions |
PubMed
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env
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Maraviroc-resistant gp120 interacts much less efficiently with CCR5 and becomes critically dependent on the V3 loop-CCR5 N terminus and on positively charged elements of the drug-modified CCR5 extracellular loops 1 (His 88) and 2 (His 181) |
PubMed
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env
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HIV-1-induced cell fusion is mediated by multiple regions within both the viral gp120 protein and the CCR5 coreceptor; dual-tropic virus isolates are less tolerant to changes in CCR5 than macrophage-tropic strains that have more restricted coreceptor use |
PubMed
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env
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HIV-1 gp120 from a T-cell-tropic virus causes CD4-dependent antagonism of CXCR4 response to SDF-1alpha, whereas gp120 from macrophage-tropic viruses causes CD4-dependent antagonism of CCR5 response to MIP-1alpha |
PubMed
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env
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HIV-1 gp120 induced cell death is inhibited by a CCR5-mediated neuroprotective pathway that involves protein kinase Akt/PKB as an essential component and can be triggered by the CCR5 agonists MIP-1beta and RANTES |
PubMed
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env
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HIV-1 gp120-induced neuronal cell death involves p38 mitogen-activated protein kinase; both HIV-1 coreceptors, CCR5 and CXCR4, can mediate HIV-1 gp120-induced neurotoxicity |
PubMed
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env
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The HIV-1 envelope protein gp120 from macrophage-tropic HIV and SIV induces a signal through CCR5 on CD4+ T cells and macrophages, and this gp120-mediated signal transduction induces chemotaxis of T cells |
PubMed
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env
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An adapted primary HIV-1 isolate, ADA, is able to replicate in CD4-negative cells expressing human CCR5; the gp120 glycoprotein of the adapted virus binds CCR5 directly, without prior interaction with CD4 |
PubMed
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env
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Membrane fusion inhibitors inhibit HIV-1 infection in T cells by preventing gp120 interaction with CCR5 |
PubMed
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env
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HIV-1 gp120 and alcohol increase the permeability of the blood-brain barrier (BBB) model, but do not result in a significant synergistic effect. Gp120 permeability involves chemokine receptor CCR5 |
PubMed
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env
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HIV-1 gp120 and gp41-mediated virus-cell fusion is more dependent on viral core maturation for viruses bearing CXCR4-tropic gp120 than for those bearing CCR5-tropic gp120 |
PubMed
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env
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The V3 domain of HIV-1 gp120 induces associations between CD4 and CCR5 receptors in cholesterol-rich microenvironments |
PubMed
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env
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Stimulation of human monocyte-derived macrophages with HIV-1 gp120 results in the CCR5-mediated activation of Lyn and the concomitant Lyn-dependent activation of the mitogen-activated protein (MAP) kinase ERK-1/2, which leads to production of TNF-alpha |
PubMed
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env
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A peptide fragment corresponding to the loop between the fifth and sixth transmembrane regions of the CCR5 receptor (amino acids 222-240) can inhibit HIV-1 infection of MT-4 cells, suggesting this region of CCR5 is involved with HIV-1 gp120 binding |
PubMed
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env
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A synthetic peptide corresponding to amino acid residues 414-434 of HIV-1 gp120 downregulates the expression and function of chemokine receptors CCR5 and CXCR4 in monocytes by activating the 7-transmembrane G-protein-coupled receptor FPRL1/LXA4R |
PubMed
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env
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Chemokines such as MCP-3 and MCP-2 that can compete with high affinity for MIP-1beta binding to CCR5 can also compete for monomeric HIV-1 gp120 binding to CCR5, although with variable potencies |
PubMed
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env
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The chemokine receptor CCR5 is posttranslationally modified 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 |
PubMed
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env
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N-formyl-methionyl-leucylphenyl-alanine binding to formyl peptide receptor (FPR) results in significant attenuation of cell responses to CCR5 ligands and in inhibition of HIV-1 gp120-mediated fusion and infection of cells expressing CD4, CCR5, and FPR |
PubMed
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env
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HIV-1 gp120 from both CCR5- and CXCR4-tropic HIV-1 strains opens calcium-activated potassium (K(Ca)), chloride, and calcium-permeant nonselective cation channels in macrophages; these signals are mediated by CCR5 and CXCR4 |
PubMed
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env
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AGP inhibits the binding of the HIV-1 gp120 consensus V3 domain (V3Cs) and macrophage inflammatory protein-1beta (MIP-1beta) to CCR5 on human monocyte-derived macrophages (MDM) |
PubMed
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env
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CCR5 and CXCR4 coreceptor engagement by HIV-1 gp120 in primary macrophages activates 2 members of the mitogen-activated protein kinase (MAPK) superfamily, c-Jun amino-terminal kinase and p38 MAPK |
PubMed
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env
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HIV-1 gp120 interactions with CXCR4 and CCR5 lead to the cross-desensitization of CCR6 and CCR7; this gp120-induced inhibition is strictly dependent on CXCR4 or CCR5 and lipid rafts but not on CD4 or V(H)3-expressing BCR |
PubMed
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env
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Engagement of the CCR5 and CXCR4 receptors by HIV-1 gp120 induces tyrosine phosphorylation of the protein tyrosine kinase Pyk2 |
PubMed
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Envelope surface glycoprotein gp160, precursor
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env
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Interaction of the trimeric gp140 with CCR5 coreceptor triggers dendritic cells (DCs) to migrate between intestinal epithelial cells to sample virions and transfer infection to target cells |
PubMed
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Envelope transmembrane glycoprotein gp41
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env
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Primary human T cells exposed to HIV gp41 increase CCR5 mRNA expression |
PubMed
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env
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SMS2, but not SMS1, is involved in enhancement of HIV-1 gp120/gp41-mediated membrane fusion through CD4 receptor and CCR5/CXCR4 coreceptors |
PubMed
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env
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The binding of soluble TLR2 to HIV-1 MA, CA, or gp41 inhibits the nuclear translocation of NFKB p65 subunit and downregulates IL-8 and CCR5 expression, leading to inhibition of HIV-1 infection in cells |
PubMed
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env
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HIV-1 gp120 and gp41 form a transitional complex with the CD4 receptor and CCR5/CXCR4 coreceptors during virus-cell and cell-cell membrane fusion |
PubMed
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env
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HIV-1 gp120/41 Envelope proteins form a complex with integrin alpha4beta7 and chemokine receptor CCR5 on the CD4-negative gamma-delta T cell membrane, which leads to activation of the p38-caspase pathway and induces the death of gamma-delta cells |
PubMed
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env
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HIV-1 R5-tropic Env-mediated apoptosis of bystander cells is dependent on both CCR5 expression levels and fusogenic activity of the Env glycoprotein through the mechanism of apoptosis involved caspase-3 activation and mitochondrial depolarization |
PubMed
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env
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Sequences in the gp41 transmembrane (TM) can modulate coreceptor specificity and that Env sequences other than that of V3 may facilitate efficient CXCR4-mediated entry |
PubMed
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env
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Peptide P5 (residues 628-683), comprising the entire membrane proximal region of HIV-1 gp41 and its calcium-binding site, inhibits HIV-1 envelope mediated cell-cell fusion and infection of PBMCs by both X4- and R5-tropic HIV-1 strains |
PubMed
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env
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RANTES, MIP-1beta, and anti-CD4 antibodies inhibit CCR5-dependent cell-cell fusion mediated by HIV-1 gp120 and gp41 from macrophage-tropic isolates |
PubMed
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env
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Secretion of IL-10 is upregulated by HIV-1 gp41 in monocytes through activation of cAMP/adenylate cyclase and p70 (S6)-kinase; up-regulation of IL-10 is paralleled by an enhanced expression of the chemokine receptor CCR5 |
PubMed
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env
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HIV-1 gp41 activates innate host immune cells through FPRL1, and the activation of FPRL1 by gp41 further induces the phosphorylation of the chemokine receptor CCR5 |
PubMed
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Nef
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nef
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HIV-1 Nef expression from unintegrated HIV-1 DNA downregulates the surface levels of CD4, CCR5, and CXCR4 on T-lymphocytes and monocytes |
PubMed
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nef
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HIV-1 Nef downregulates cell-surface levels of CCR5 in CHO cells expressing human CCR5; the Nef-induced downregulation of CCR5 is as efficient as the downregulation induced by the natural beta-chemokine ligand RANTES |
PubMed
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nef
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SH3 (PxxP motif) and PACS (E4) interaction surfaces as well as the myristoylation site (G2) in HIV-1 Nef are required for Nef-mediated downregulation of CCR5 |
PubMed
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Tat
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tat
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HIV-1 Tat upregulates CCR5 expression on monocytes/macrophages but not on lymphocytes, indicating a role for Tat in HIV-1 pathogenesis and in promoting the infection of monocytes/macrophages. |
PubMed
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tat
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Results from the treatment of microglia with HIV-1 Tat suggest downregulation of CCR5 mRNA expression by HIV-1 Tat, however this was deemed to not be significant |
PubMed
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tat
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HIV-1 Tat is associated with upregulation of CCR5 and MIP-1alpha expression in nodular lesions found in HIV encephalopathy and progressive multifocal leukoencephalopathy (PML), indicating a role for Tat in HIV-1 pathogenesis |
PubMed
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Vpr
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vpr
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HIV-1 Vpr depletes regulatory CD4+ T cells and enhances HIV-1 replication in a CCR5 coreceptor-dependent manner |
PubMed
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capsid
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gag
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Primary human T cells exposed to HIV CA (p24) increase CCR5 mRNA expression |
PubMed
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gag
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Herpes simplex virus type 2-Infected monocyte-derived dendritic cells (MDDCs) produce TNF-alpha, which binds to its receptor TNF-R1 and upregulates the expression of CCR5 on cell surface, leading to enhance HIV-1 p24 release from MDDCs |
PubMed
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gag
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The binding of soluble TLR2 to HIV-1 MA, CA, or gp41 inhibits the nuclear translocation of NFKB p65 subunit and downregulates IL-8 and CCR5 expression, leading to inhibition of HIV-1 infection in cells |
PubMed
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matrix
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gag
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Exposure of primary human T cells to HIV MA (p17) increases CCR5 mRNA expression |
PubMed
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gag
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The binding of soluble TLR2 to HIV-1 MA, CA, or gp41 inhibits the nuclear translocation of NFKB p65 subunit and downregulates IL-8 and CCR5 expression, leading to inhibition of HIV-1 infection in cells |
PubMed
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