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Envelope surface glycoprotein gp120
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env
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HIV-1 HXB2 Env binds and fuses to CV-1 cells expressing CD4 and CXCR4 |
PubMed
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env
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HIV-1 JR-CSF Env mutant E153G binds CD4 with better affinity |
PubMed
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env
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HIV-1 Env (gp120) binds to CD4 and is destabilized by lysine based dendrimer SPL7013 |
PubMed
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env
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HIV-1 Envs utilize CD4/CCR5 with different efficiences according to subtype designation (A, B, C and D) |
PubMed
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env
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HIV-1 Env (gp120) binds to CD4 through in silico analysis |
PubMed
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env
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Human C"" beta strand (amino acids 42-47) of CD4, particularly Phe-43, plays a crucial role in HIV-1 coreceptor function as well as in HIV-1 gp120-CD4 binding capacity |
PubMed
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env
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HIV-1 envelope glycoprotein gp120 binds to the cell surface receptor CD4 or soluble CD4; the carbohydrates present on gp120 are necessary for CD4 binding during HIV-1 entry |
PubMed
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env
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HIV-1 Env (ADA) mutation N197S confers independence from CD4-mediated HIV-1 entry in to host cells |
PubMed
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env
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HIV-1 Env (NL4-3) conformational dynamics and states are stabilized by soluble CD4 [and the coreceptor surrogate antibody 17b] |
PubMed
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env
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Enhanced CD4 binding activity of HIV-1 isolate R3A gp120/gp41 contributes to activate plasmacytoid dendritic cells (pDCs) |
PubMed
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env
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HIV-1 gp120 interacts with CD4 and CXCR4 to enhance CCR7-dependent human CD4+ T cell migration |
PubMed
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env
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HIV-1 gp120 enhances CCL-21-induced CD4+ T cell chemotaxis in a CXCR4- and CD4-dependent manner |
PubMed
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env
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HbAHP-25, an analogue of Hb-alpha derived peptide, inhibits CCR5-tropic and CXCR4-tropic HIV-1 strains by blocking the binding of CD4 to HIV-1 gp120 and the subsequent steps leading to entry and/or fusion |
PubMed
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env
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Soluble CD4 can bind to HIV-1 gp120 and block HIV-1 infectivity |
PubMed
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env
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Anti-CD4 antibodies are capable of neutralizing HIV-1 strains or blocking the binding of HIV-1 envelope glycoprotein gp120 and cell surface receptor CD4 |
PubMed
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env
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HIV-1 gp120 with T257S/S375W double mutation is stabilized into the CD4-bound state, with increasing relative fixation between core, full-length monomeric, and full-length trimeric versions of gp120 |
PubMed
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env
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CD4 binding results in a major reorganization of the gp120 trimer, causing an outward rotation and displacement of each gp120 monomer |
PubMed
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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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CXCR4, a 45kDa cellular membrane protein, interacts with the cell surface HIV-1 gp120-CD4 complex and acts as a coreceptor to preferentially support T cell line-tropic HIV-1 Env-mediated cell fusion and HIV-1 infection |
PubMed
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env
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Monoclonal antibodies (MAbs) to defined peptide epitopes or N-linked glycans in HIV-1 gp120 inhibit the binding of gp120 to CD4 and exhibit neutralizing activities against HIV-1 |
PubMed
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env
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Divergent HIV-1 strains differ in their stoichiometry of entry and require between 1 to 7 HIV-1 gp120/gp41 trimers, with most strains depending on 2 to 3 trimers to complete entry through the interaction with CD4 |
PubMed
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env
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Two independent mutations in HIV-1 subtype A gp120, G312V (V3 loop) and A204E (C2 region), are identified to gain increased affinity to soluble CD4 compared to the wild-type |
PubMed
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env
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Some synthetic peptides as agonists of the HIV-1 envelope glycoprotein gp120 or CD4 receptor block the binding of gp120 and CD4; other peptides do not block the binding between gp120 and CD4 |
PubMed
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env
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Using single-molecule fluorescence resonance energy transfer within the context of native gp120 trimers on the surface of HIV-1 virions, indicates a significant conformational change between unliganded and CD4-binding trimers |
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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CD4 binding to HIV-1 gp120/gp41 trimers results in significant conformational changes in M150 and M161 in gp120 V1/V2 and F316 in gp120 V3, but causes little changes in M104, M95, and the triad of gp41 leucines |
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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The net charge of HIV-1 gp120 V3 loop influences the global structure and diversity of the interaction surface of the gp120 outer domain to CD4 binding and epitopes exposure |
PubMed
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env
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HIV-1 gp120 interacts with CD4 and alpha5beta3 in peripheral blood monocyte-derived macrophages; neutralizing antibodies against the alpha5beta3 integrin interfere with the coprecipitation of alpha5beta3 with an anti-gp120 antibody |
PubMed
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env
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CD4 binding residues T257, E370, S375, N425, G429, and G473 of HIV-1 gp120 are involved in NBD analogues interaction with gp120 |
PubMed
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env
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The Cryo-EM structure shows that localization at the gp120-gp41 interface allows the fusion peptide region to be released in response to CD4 and co-receptor-induced conformational changes within gp120 and gp41 that drive membrane fusion |
PubMed
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env
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HIV-1 gp120 is incapable of binding a fully oxidized, monomeric 2dCD4 in which both domain 1 and 2 disulfides are intact, but binds to reduced counterparts that are the ostensible products of Trx-mediated isomerization |
PubMed
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env
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Deletion of both HIV-1 nef and vpu genes enhance a significant engagement between HIV-1 gp120 and CD4 at the cell surface, suggesting Nef and Vpu prevent the exposure of epitopes recognized by anti-gp120 antibody-dependent cell-mediated cytotoxicity |
PubMed
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env
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HIV-1 gp120 is sulfated at positions Y173 and Y177 in the V2 domain by tyrosyl sulfotransferase 2 (TPST2), leading to modulate gp120 epitope exposure and neutralization sensitivity to soluble CD4 |
PubMed
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env
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The ability of thioredoxin, a protein disulfide isomerase (PDI), to reduce the disulfide bond in CD4 is enhanced in the presence of HIV-1 gp120 |
PubMed
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env
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Small molecules exhibit strong anti-HIV-1 activity by binding specifically to both HIV-1 gp120 and/or cell surface receptors (CD4, CCR5, CXCR4) and prevent gp120/CD4/CCR5 and gp120/CD4/CXCR4 complex formation and cell-cell fusion |
PubMed
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env
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The interaction between exposed cyclophilin A (CypA) and cell surface heparans represents the initial step of HIV-1 attachment and is a necessary step for HIV-1 gp120 binding to CD4 |
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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Protein-disulfide isomerase (PDI) cleaves disulfide bonds in recombinant HIV-1 envelope glycoprotein gp120, and gp120 bound to the surface receptor CD4 undergoes a disulfide reduction that is prevented by PDI inhibitors |
PubMed
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env
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Binding of recombinant soluble CD4 (sCD4), the purified V1 domain of sCD4, or neutralizing antibodies to the HIV-1 surface glycoprotein gp120 on virions results in rapid dissociation of gp120 from its complex with the transmembrane glycoprotein gp41 |
PubMed
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env
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A high affinity interaction between the HIV-1 glycoprotein gp120/gp41 complex and the cellular receptor CD4 is necessary for both virus-cell and cell-cell fusion; the V3 region (amino acids 301-336) of gp120 and gp41 amino terminus are involved in fusion |
PubMed
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env
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HIV-1 gp120 induces the dissociation of p56lck from CD4 and the downregulation of CD4 from the cellular surface |
PubMed
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env
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The layer 3 residues (amino acids 247-254 and 476-483) of HIV-1 gp120 are located in the beta8 strand and alpha5 helix of the CD4-bound gp120. The five layer 3 mutants T248A, H249A, R476A, N478A, and W479A exhibit decreased CD4-binding activity |
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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CD4-mediated endocytosis of HIV-1 gp120 results in MHC-II (HLA-DR) presentation to CD4+ T cells |
PubMed
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env
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Immature HIV-1 virions are competent for CD4-induced gp120 conformational changes |
PubMed
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env
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HIV-1 gp120-mediated inhibition of IFN-alpha production involves CD4 and BDCA2 in plasmacytoid dendritic cells |
PubMed
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env
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CD4 binding shifts the V1/V2 regions of HIV-1 gp120 to unmask the co-receptor binding site, and triggers profound dynamic changes in gp120 spanning from the binding site to the gp41-interactive face of gp120 |
PubMed
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env
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Brain-derived HIV-1 Env gp120 proteins efficiently use very low levels of CD4 to enter cells, whereas lymph-node-derived gp120 proteins are dependent on higher levels of CD4 to enter cells |
PubMed
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env
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N425K mutation of HIV-1 gp120 impacts CD4 interactions and confers HIV-1 resistance to maraviroc (MVC) |
PubMed
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env
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Small molecule BMS-488043 inhibits the interaction of HIV-1 gp120 with CD4 by blocking the rotation of the Trp112 located on the alpha1 helix of gp120 |
PubMed
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env
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CD4-linker-DC-SIGN fusion proteins enhance binding affinity to HIV-1 gp140 and gp120 in comparison to sCD4 and sDC-SIGN. These fusion proteins inhibit HIV-1 capture and transfer via DC-SIGN-expressing cells and iMDDCs |
PubMed
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env
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HIV-1 induces an elongated phenotype in infected CD4+ T cells. These HIV-infected T cells tether to other lymph node CD4+ cells and form syncytia through gp120/gp41, and migrate to distant tissues to disseminate |
PubMed
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env
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The N260Q gp120 mutant has a significantly lower binding to the recombinant soluble CD4 in comparison with wild-type |
PubMed
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env
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Human alpha-defensin-5 binds to both HIV-1 gp120 and CD4 and blocks the interaction of CD4 with gp120, which leads to inhibit HIV-1 replication in human primary CD4+ T lymphocytes |
PubMed
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env
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Feglymycin, a natural Streptomyces-derived 13mer peptide, inhibits HIV-1 gp120 binding to CD4 |
PubMed
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env
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A single Y681H substitution in HIV-1 gp41 increases the gp120-CD4 binding and enhances infectivity in low CD4 expressing cells |
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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Association and clustering of CD4-CXCR4 induced by HIV-1 gp120 requires moesin-mediated anchoring of actin in the plasma membrane |
PubMed
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env
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Interaction of the X4-tropic protein HIV-1 gp120 with CD4 augments ezrin and moesin phosphorylation in human permissive T cells, thereby regulating ezrin-moesin activation |
PubMed
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env
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HIV-1 gp120 isolated from southern African HIV type 1 subtype C exhibits high-affinity binding to CD4 and the Cys228-Cys239 disulfide bond of gp120 is required for the high-affinity binding to CD4 |
PubMed
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env
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Antibodies to LFA-3 block the early stages of HIV-1 infection by cell-free virus following HIV-1 gp120 binding to CD4 |
PubMed
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env
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The binding of HIV-1 gp120 to CD4 molecules on T cells interrupts the sequential cascade of intercellular interactions involving antigen/MHC class II-TCR/CD4, CD40L-CD40, and B71-CD28 |
PubMed
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env
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Alpha-defensins inhibit the binding of HIV-1 gp120 to CD4 through interaction with the D1 domain of CD4 |
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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Binding gp140 to the synthetic CD4-mimicking mini protein leads to an outward domain shift of the three gp120 subunits, which diminishes gp120-gp41 interactions |
PubMed
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env
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D279 in the C2 region and N362 in the C3 region of HIV-1 gp120 augment the gp120-CD4 interaction |
PubMed
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env
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HIV-1 gp120 drastically reduces the ratio of CD4 dimers/monomers |
PubMed
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env
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Maleic anhydride-modified ovalbumin inhibits HIV-1 entry by targeting both gp120 on HIV-1 virions and CD4 receptor on the host cells |
PubMed
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env
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Palmitic acid analog 2-bromopalmitate (2-BP) efficiently binds to CD4 leading to the inhibition of gp120-to-CD4 binding |
PubMed
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env
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HIV-1 gp120 interacts with CD4 to cause apoptosis in human mesenchymal stem cells |
PubMed
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env
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A fusion of the CD4- and CCR5-mimetic peptides, DM1, binds gp120 and neutralizes R5, R5X4, and X4 HIV-1 isolates comparably to CD4 |
PubMed
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env
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Griffithsin (GRFT) interaction with gp120 exposes the CD4 binding site by binding the glycan at position 386 |
PubMed
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env
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Sphingomyelinase inhibits viral fusion after the engagement of HIV-1 gp120 with CD4 and this inhibition is dependent on CD4 expression levels |
PubMed
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env
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Tick salivary protein Salp15 prevents gp120-CD4 interaction at least partially through its direct interaction with the envelope glycoprotein in the C1 domain of gp120 |
PubMed
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env
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Competition assays with CD4 and mAbs suggest that SP-A inhibits infectivity by occlusion of the CD4-binding site on gp120 |
PubMed
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env
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In resting CD4 T cells, only the HIV envelope-mediated entry, but not the VSV-G-mediated endocytosis, can lead to viral DNA synthesis and nuclear migration |
PubMed
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env
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In a CD4-bound state, gp120 elements proximal to the gp41 interface complete a 7-stranded beta-sandwich, which appeared invariant in conformation |
PubMed
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env
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Co-expression of CD4 and DC-SIGN in Raji cells promotes internalization and intracellular retention of HIV-1 through interaction with HIV-1 gp120 |
PubMed
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env
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Expression of CD4 on Raji B cells strongly inhibits DC-SIGN-mediated HIV-1 transmission to T cells, presumably through interaction with HIV-1 gp120 |
PubMed
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env
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CCR5- or CXCR4-tropic HIV-1 induce Indoleamine 2,3-dioxygenase (IDO) in plasmacytoid dendritic cells and this induction is inhibited by the blockade of gp120/CD4 interactions with antibodies to CD4 |
PubMed
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env
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Substitution of highly conserved isoleucine with methionine at position 424 in the C4 domain of gp120 confers enhanced neutralization sensitivity to plasma antibodies and increases its interaction with sCD4 but not with CCR5 |
PubMed
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env
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HIV-1 infections originating from cell-free virus by CD4/gp120 interactions decrease strongly in the presence of antiretrovirals tenofovir and efavirenz whereas infections involving cell-to-cell spread are markedly less sensitive to the drugs |
PubMed
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env
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Bile salt-stimulated lipase (BSSL), a Lewis X (LeX)-containing glycoprotein found in human milk, binds to DC-SIGN and inhibits the interaction of gp120 with CD4 |
PubMed
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env
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The disulfide cross-linking interaction between gp120 and PDI is enhanced by CD4 protein |
PubMed
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env
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Focal adhesion kinase (FAK), CD4, and HIV-1 gp120 co-localize in T cells. The formation of FAK-CD4 complex is induced by gp120 |
PubMed
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env
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Epigallocatechin gallate (EGCG) purified from the green tea catechin inhibits attachment of HIV-1 glycoprotein 120 to the CD4 molecule on T cells |
PubMed
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env
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H66N change in gp120 stabilizes the HIV-1 envelope glycoprotein complex once the CD4-bound state is achieved and decreases the probability of CD4-induced inactivation |
PubMed
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env
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Two potentially flexible topological layers (layers 1 and 2) in the gp120 inner domain (layer 1-layer 2) interactions strengthen gp120-CD4 binding by reducing the off rate when CD4 makes initial contact with the gp120 outer domain |
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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Virions carrying both HIV-1 R5 env and VSV-G can fuse to naive CD4+ T cells because CD4 binding allows viral uptake |
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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Studies by sequential (SAP) and competitive (CAP) antigen panning methodologies show that some antibodies bind better to gp120-CD4 complexes than to gp120 alone |
PubMed
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env
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The ability of gp120 to inhibit SDF-1alpha-induced chemotaxis is mediated by the CD4 receptor and Lck signaling |
PubMed
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env
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Subtype C gp120 isolates carrying I309L enhance utilization of CD4 but do not affect the ability to use CCR5 |
PubMed
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env
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Virological synapse-mediated cell-to-cell HIV-1 transfer is dependent upon gp120/gp41 and CD4 interactions and is more efficient than that of a cell-free mode of uptake, yet the presence of the full CD4 cytoplasmic tail is not essential for the process |
PubMed
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env
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Siva-1 sensitizes CD4-positive T-cells to HIV-1 gp120/gp41-induced apoptosis. The Siva-1-mediated sensitization on CD4-positive T-cells shows significant activation of caspase-3, -8, and -9 |
PubMed
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env
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The V1-V3 region of a brain-derived HIV envelope glycoprotein plays a crucial role in determining the virus' low CD4 dependence and increased macrophage tropism, as well as its augmented fusogenicity and reduced sensitivity to the inhibitor BMS-378806 |
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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Deletion of the HIV-1 gp120 major variable regions (V1/V2/V3) stabilizes gp120 core proteins into the conformation recognized by CD4 |
PubMed
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env
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A synthetic CD4-mimetic peptide conjugating with a heparan sulfate dodecasaccharide binds to gp120 and induces the exposure of the coreceptor binding domain available for interaction with the oligosaccharide |
PubMed
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env
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HIV-1 gp120 promotes filamin binding to both CD4 and CXCR4 |
PubMed
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env
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CIITA-mediated enhancement of HIV-1 infection is gp120/gp41/CD4-dependent and occurs at the early steps in the infection cycle |
PubMed
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env
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Elimination of the CD4 domain 2 disulfide bond (Cys130-Cys159) by mutation enhances HIV-1 gp120/gp41-mediated cell-cell fusion and virus entry |
PubMed
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env
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Thioredoxin cleaves the gp120 disulfide bond (Cys296-Cys331) in the V3 domain and the cleavage is enhanced by CD4-expressing cells |
PubMed
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env
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The cis expression of DC-SIGN on multiple lymphoid cell lines enables more efficient entry and replication of CXCR4-tropic and CCR5/CXCR4 dual-tropic HIV-1 through its binding to the HIV-1 gp120-CD4-CXCR4 complex |
PubMed
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env
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HIV-1 gp120 specifically recognizes the C-terminal heparin-binding domain of fibronectin (Fn) and this binding inhibits the interaction of gp120 with soluble CD4 |
PubMed
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env
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Apoptosis of CD4+ lymphocytes induced by HIV-1 gp120 cross-linking to CD4 is inhibited by IL-12 |
PubMed
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env
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HIV-1 envelope glycoproteins gp120 and gp160 directly and specifically impair the CD3/TcR-mediated activation of phospholipase C (PLC) via the CD4 molecule in uninfected T cells |
PubMed
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env
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Galectin-1, a dimeric beta-galactoside-binding protein, promotes infection with CCR5-tropic, CXCR4-tropic, and CCR5/CXCR4 dual-tropic HIV-1 variants by facilitating attachment of HIV-1 gp120 to CD4 at the cell surface |
PubMed
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env
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The binding of HIV-1 gp120 to CD4+-permissive cells increases the level of acetylated alpha-tubulin in a CD4-dependent manner; overexpression of Histone Deacetylase 6 (HDAC6) inhibits the acetylation of alpha-tubulin and prevents HIV-1-cell fusion |
PubMed
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env
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Griffithsin isolated from an aqueous extract of the red alga Griffithsia species blocks CD4-dependent HIV-1 gp120 binding to receptor-expressing cells and binds to viral coat glycoproteins (gp120, gp41, and gp160) in a glycosylation-dependent manner |
PubMed
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env
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HIV-1 gp120-CD4 interaction is necessary to repress HIV-1 long terminal repeat-dependent luciferase activity; the cytoplasmic domain of CD4 is found to be required for this effect to occur |
PubMed
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env
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Binding of HIV-1 gp120 to CD4 molecules in cells results in the association of Lck and Raf-1, which is abolished by preincubation of the virus with soluble CD4 |
PubMed
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env
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The fusion of insulin-like growth factor I (IGF I) with stromal cell-derived factor I or alpha1 proteinase inhibitor has the capacity to compete with the binding of HIV-1 gp120 to CD4 receptor |
PubMed
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env
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Phorbol myristate acetate (PMA) pretreatment of CD4+ cells prevents subsequent HIV-1 gp120-induced downregulation of CD4 receptor molecules |
PubMed
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env
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Expression of the HIV-1 envelope gene in CD4+ T cell lines and binding of HIV-1 gp120 to CD4 is sufficient for the induction of apoptosis |
PubMed
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env
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Combinations of CD4-based molecules and antibodies to HIV-1 gp120 and/or gp41 inhibit cell fusion formation mediated by the interaction of CD4 to gp120 |
PubMed
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env
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Following incubation with a soluble form of CD4, gp120 of highly purified HIV-1 preparations is cleaved without addition of exogenous proteinase, yielding two proteins of 50 and 70 kDa; this cleavage likely occurs in the gp120 V3 loop |
PubMed
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env
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Mutants with amino acid changes in the V1/V2 region (residues 131-196) of the HIV-1 gp120 are able to bind CD4 but are deficient in syncytium formation and/or virus entry |
PubMed
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env
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Release of neurotoxins from monocytes through HIV-1 gp120 stimulation involves CD4 receptors; toxin production can be inhibited either by a monoclonal antibody to the CD4-binding region of gp120 or by soluble CD4 receptors |
PubMed
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env
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Calcium ions are required for cell fusion mediated by interactions between CD4 and HIV-1 gp120/gp41; EDTA and EGTA block cell fusion in culture media containing calcium ions |
PubMed
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env
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The third complementarity-determining region (CDR3; residues 79-96) within domain 1 of the human CD4 molecule plays a critical role in membrane fusion mediated by the interaction of CD4 with HIV-1 gp120 |
PubMed
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env
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Binding of HIV-1 gp120 to the CD4 receptor molecule results in co-stimulation of CD3-induced T cell activation |
PubMed
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env
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HIV-1 gp120-mediated CD4 engagement is involved in the induction of susceptibility of primary human T lymphocytes to CD95-mediated apoptosis through ezrin phosphorylation and ezrin-to-CD95 association |
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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The inhibition of IL-2R expression and proliferation induced by the interaction of CD4 with HIV-1 envelope glycoprotein gp120 is correlated with the inhibition of expression and activation of Janus kinase JAK3 |
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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A specific interaction between CD4 and HIV-1 gp120 is required for phosphorylation of CD4, which could involve protein kinase C |
PubMed
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env
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Amino acid residues 42-49 and 54-57 in the V1 region of CD4 are involved in the interaction of CD4 with both HIV-1 gp120 and class II major histocompatibility complex molecules |
PubMed
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env
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Mutations at four locations (amino acids 29, 59-64, 77-81, and 85) outside the antigen-complementarity-determining region (CDR2)-like sequence of CD4 markedly affect HIV-1 gp120 binding |
PubMed
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env
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Removal of the N-linked sugars on HIV-1 gp120 by endoglycosidase H treatment results in deglycosylated proteins that are unable to bind to CD4, suggesting that glycosylation contributes to the ability of gp120 to bind to CD4 |
PubMed
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env
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Deletion analysis shows that amino acid regions 82-95, 386-389, 424-432, and 487-499 constitute a part of the HIV-1 gp120 binding region to CD4 |
PubMed
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env
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HIV-1 gp120/160 deglycosylated by Endo H and Endo F still binds to CD4, indicating that the carbohydrates of gp120/160 do not play a significant role in the in vitro binding to CD4 |
PubMed
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env
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HIV-1 gp120 suppresses T and B cell activation and the expression of cytolytic activities through its interaction with CD4 |
PubMed
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env
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HIV-1 gp120 and class II MHC binding sites of CD4 are distinct and can be separated |
PubMed
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env
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A single amino-acid change (cysteine 402 or tryptophan 432) in HIV-1 gp120 can abrogate CD4 binding |
PubMed
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env
|
Apoptosis induced by HIV-1 gp120/CD4 cross-linking in Th1 clones is inhibited by anti-CD95 or anti-CD95L neutralizing monoclonal antibodies, as well as by a specific interleukin-1 beta converting enzyme (ICE) inhibitor |
PubMed
|
|
env
|
IL-16 induces rapid translocation of PKC from the cytosol to the membrane in CD4+ cells; PKC inhibitors completely block IL-16-induced lymphocyte migration as well as the motile response induced by HIV-1 gp120 and anti-CD4 antibody binding to CD4 |
PubMed
|
|
env
|
CD4 downregulation by the treatment of macrophages with HIV-1 gp120 is mediated through the induction of endogenous TNF-alpha |
PubMed
|
|
env
|
A CD4 peptide (amino acids 74-95) inhibits the binding of gp120 to CD4+ human lymphoblastic leukemia (CEM) cells |
PubMed
|
|
env
|
Through binding to cell surface CD4, both HIV-1 gp120 and gp160 inhibit syncytia formation between HIV-1-infected cells and CD4+ cells |
PubMed
|
|
env
|
Chimpanzee CD4 molecules bearing the human amino acid at position 87 support syncytium formation, while human CD4 molecules bearing the chimpanzee residue at position 87 do not; HIV-1 gp120 binding to CD4 is not affected by the substitution at position 87 |
PubMed
|
|
env
|
Expression of a soluble CD4 mutant molecule lacking transmembrane and cytoplasmic domains blocks secretion of HIV-1 gp120 and surface expression of HIV-1 gp120 and gp41 from the endoplasmic reticulum |
PubMed
|
|
env
|
Small molecules, termed N-carbomethoxycarbonyl-prolyl-phenylalanyl benzyl esters (CPFs), block the binding of gp120 to CD4, but do not interfere with the binding of CD4 to class II major histocompatibility complex molecules |
PubMed
|
|
env
|
HIV-1 gp120 with substitution of cysteine's 296, 331, 418 or 445 on fails to bind to CD4 |
PubMed
|
|
env
|
The N-terminal region of HIV-1 gp120 contains conserved residues (amino acids 56-62 and 108-116) critical for binding to CD4 |
PubMed
|
|
env
|
Changes in two hydrophobic regions (Thr-257 and Trp-427) and two hydrophilic regions (Asp-368, Glu-370, and Asp-457) of HIV-1 gp120 result in significant reductions in CD4 binding |
PubMed
|
|
env
|
Expression of the human CD4 receptor in murine T-cells is sufficient for syncytia formation with HIV-1 envelope expressing cells and entry of MLV/HIV pseudotyped retroviral vectors, suggesting that the murine CXCR4 is a functional coreceptor |
PubMed
|
|
env
|
CD4(+)CD45RO(+) cells display high HIV-1 gp120-binding capacity, whereas CD4(+)CD45RO(-) cells show undetectable HIV-1 gp120 binding |
PubMed
|
|
env
|
The physiological levels of cell-surface CD4 interfere with HIV-1 replication in T cells by a mechanism that inhibits HIV-1 gp120 envelope incorporation into viral membranes |
PubMed
|
|
env
|
Syncytial apoptosis mediated by the fusion of cells expressing HIV-1 gp120 with cells expressing the CD4/CXCR4 receptor/coreceptor complex causes phosphorylation of p53 on serine 15 and Bax upregulation |
PubMed
|
|
env
|
Mutation of two basic amino acids Lys46 and Arg59 in CD4 dramatically disrupts its ability to bind HIV-1 gp120 |
PubMed
|
|
env
|
CD4-expressing human T cell lines induce significant and rapid conformational changes in gp120-gp41 from T cell-tropic HIV-1 strains, and little conformational changes in gp120-gp41 from macrophage-tropic HIV-1 strains |
PubMed
|
|
env
|
Binding of HIV-1 gp120 to CD4 receptor induces p56lck activation and zeta-chain (TCR) associated protein kinase 70kDa desensitization independent of TCR tyrosine phosphorylation |
PubMed
|
|
env
|
Pretreatment of HIV-1 infected cells with TNF alpha augments syncytia formation mediated by the interaction of HIV-1 gp120 with cell surface CD4 molecules |
PubMed
|
|
env
|
Interaction of HIV-1 gp120 with cell-associated CD4 leads to the induction of IFN alpha; preincubation of cells with anti-CD4 or the presence of soluble CD4 during incubation inhibits IFN alpha induction |
PubMed
|
|
env
|
Cleavage at position R315 of HIV-1 gp120 by thrombin is enhanced by soluble CD4 binding |
PubMed
|
|
env
|
Two disulfide bonds linking cysteine residues at positions 378 and 445 and positions 385 and 418 in the carboxyl terminus of HIV-1 gp120 contribute to CD4 binding |
PubMed
|
|
env
|
Amino acid residues (102-126) and (425-452) of HIV-1 gp120 contribute to the binding site for CD4 and are expected to be juxtaposed in the folded gp120 chain |
PubMed
|
|
env
|
Crosslinking of HIV-1 gp120 on human CD4+ T cells followed by signaling through the TCR results in activation-induced apoptosis |
PubMed
|
|
env
|
LFA-1 adhesion molecules are not involved in the early stages of cell membrane fusion mediated by the interaction of gp120 with CD4 |
PubMed
|
|
env
|
Down modulation of the interaction between HIV-1 gp120 and CD4 by TPA is blocked by protein kinase C (PKC) inhibitors, suggesting PKC may play an important role in HIV-1 infection |
PubMed
|
|
env
|
12-O-tetradecanoylphorbol-13-acetate (TPA) down-modulates the expression of CD4, which is essential for syncytia formation through interaction with the HIV-1 envelope protein gp120 |
PubMed
|
|
env
|
Glycolipids such as galactosylceramides, sulfogalactoceramides, globotriosylceramide, and gangliosides play an important role as HIV-1 fusion cofactors following the interaction of CD4 and HIV-1 gp120 |
PubMed
|
|
env
|
Gross cystic disease fluid protein-15 (GCDFP-15) binds to CD4, a T-cell co-receptor involved in antigen recognition, thereby inhibiting the ability of the receptor to interact with the HIV-1 envelope protein gp120 |
PubMed
|
|
env
|
Contact of CD4+ T cells with HIV-1 infected or HIV-1 gp120-expressing cells induces PARP hydrolysis, which leads to the cleavage of 116 kDa PARP into two fragments |
PubMed
|
|
env
|
CD4-p56Lck interaction is required for HIV-1 gp120-induced nuclear translocation of NF-kappaB in HeLa cells |
PubMed
|
|
env
|
Adsorption of multivalent gp120-containing HIV-1 virion particles into CD4+ T lymphocytes results in segregation of CD4 and CXCR4 into distinct lipid micro domains |
PubMed
|
|
env
|
A fusion protein between HIV-1 gp120 hepatitis B surface antigen (HBsAg) is capable of spontaneous assembly into virus-like particles and exhibits high affinity binding to CD4 |
PubMed
|
|
env
|
Retrocyclin binds to soluble CD4 and HIV-1 gp120, colocalizes with CD4, CXCR4, and CCR5, and inhibits replication of CCR5-tropic and CXCR4-tropic strains of HIV-1 in human cells, presumably through inhibition of gp120-CD4 binding |
PubMed
|
|
env
|
The level of HIV-1 gp120-mediated syncytium formation and infectivity is enhanced in the presence of neuraminidase (NA) and involves the interaction between gp120, CD4, and chemokine coreceptors |
PubMed
|
|
env
|
CD26 (dipeptidyl peptidase IV) cleaves the highly conserved V3 loop of HIV-1 gp120 and functions as a cofactor for entry of HIV-1 in CD4+ human cells; coexpression of human CD4 and CD26 in murine NIH 3T3 cells renders them permissive to HIV-1 |
PubMed
|
|
env
|
Cells expressing a chimeric molecule consisting of the first 177 residues of CD4 attached to residues from the hinge, transmembrane, and cytoplasmic domains of CD8 are susceptible to fusion with cells expressing HIV-1 gp120 |
PubMed
|
|
env
|
Several polyanionic anti-HIV compounds, including dextran sulfate, pentosan polysulfate, heparin, aurintricarboxylic acid (ATA), suramin, and Evans blue, interact with HIV-1 gp120 to block the binding of gp120 to CD4 |
PubMed
|
|
env
|
A 287 residue variant of HIV-1 gp120 (ENV59) missing 197 amino acids binds to CD4 with high affinity |
PubMed
|
|
env
|
Cell-cell contact between T cells expressing HIV-1 gp120/gp41 and other T cells expressing CD4 receptors leads to the rapid accumulation of cyclin B and tyrosine-hyperphosphorylated p34cdc2 (cdk1) kinase, indicative of cell cycle arrest at G2 phase |
PubMed
|
|
env
|
HIV-1 envelope protein gp120 can specifically inhibit CD4-dependent class II MHC-restricted T cell response to Antigens |
PubMed
|
|
env
|
95- and 25-kDa peptides derived from the disulfide bond reduction of HIV-1 gp120 bind to human CD4 |
PubMed
|
|
env
|
The first two domains (amino acid residues 1-177) of human CD4 bind effectively to HIV-1 gp120, and most residues interacting with gp120 lie within amino acids 21-64; the COOH-terminal half of the molecule is not necessary |
PubMed
|
|
env
|
Amino acid sequences 397-439 in HIV-1 gp120 are directly involved in the binding of gp120 to the CD4 receptor |
PubMed
|
|
env
|
Cleavage of HIV-1 gp120 with trypsin at residue 432 destroys CD4 binding |
PubMed
|
|
env
|
Inhibition of HIV-1 binding to CD4 by suramin is reversed by human albumin, suggesting that only free suramin has antiviral properties |
PubMed
|
|
env
|
HIV-1 gp120 stimulates monocytes to release TNF-alpha, IL-1 beta, IL-6, and granulocyte-macrophage-CSF, and this effect can be blocked with soluble CD4 |
PubMed
|
|
env
|
T-tropic HIV-1 gp120s are capable of priming phorbol ester (PMA) induced co-down-modulation of gp120 complexes with tailless CD4 by interacting with CXCR4, whereas M-tropic gp120 are not, even in the presence of CCR5 |
PubMed
|
|
env
|
CD38 expression blocks lymphocyte susceptibility to HIV-1 infection by inhibiting HIV-1 gp120/CD4-dependent viral binding to target cells |
PubMed
|
|
env
|
HIV-1 gp120 induces CD4 association with lymphocyte surface molecules CD3, CD11a, CD27, CD45RA, CD45RB, CD45RO, CD49d, CD38, CD26, CD59, CD95 and class I MHC molecules |
PubMed
|
|
env
|
HIV-1 gp120 induces a specific phospholipase A2 (PLA2) activation in lymphocytes through binding to CD4, but this effect is not sufficient to accomplish virus/cell fusion |
PubMed
|
|
Envelope surface glycoprotein gp160, precursor
|
env
|
HIV-1 gp160 interacts with CD4; predicted interaction to be within the endoplasmic reticulum |
PubMed
|
|
env
|
HIV-1 Env gp160 downregulates CD4 from the surface of infected cells |
PubMed
|
|
env
|
HIV-1 glycoprotein gp160 binds to both cell surface receptor and soluble CD4 and the interaction of gp160 with CD4 results in virus-cell and cell-cell fusion |
PubMed
|
|
env
|
HIV-1 gp160 molecules exist predominantly as a dimer, but higher forms corresponding to trimers and tetramers are also observed; multiple CD4 molecules bind to the gp160 oligomers |
PubMed
|
|
env
|
HIV-1 heterotrimeric gp140 of inter- and intra-subtype combinations (subtype A, B, C, D and F) are shown to bind CD4 and a panel of neutralizing monoclonal antibodies with similar affinity to monovalent UG37 gp140 |
PubMed
|
|
env
|
CD4 interaction with HIV-1 Env is necessary for contact induced cytoplasmic remodeling such as mitochondria polarization in HIV-1 infected T cells |
PubMed
|
|
env
|
The double alanine mutations at HIV-1 Env positions 671 and 674 result in attenuation of Env-mediated cell-cell fusion and hemifusion, as well as viral infectivity mediated by both CD4-dependent and CD4-independent viruses |
PubMed
|
|
env
|
CD4-linker-DC-SIGN fusion proteins enhance binding affinity to HIV-1 gp140 and gp120 in comparison to sCD4 and sDC-SIGN. These fusion proteins inhibit HIV-1 capture and transfer via DC-SIGN-expressing cells and iMDDCs |
PubMed
|
|
env
|
DC-SIGN increases the binding affinity of trimeric gp140 envelope glycoproteins to CD4 on permissive cell surface |
PubMed
|
|
env
|
HIV-1 Env from subtype P downregulates CD4 cell surface expression |
PubMed
|
|
env
|
Binding gp140 to the synthetic CD4-mimicking mini protein leads to an outward domain shift of the three gp120 subunits, which diminishes gp120-gp41 interactions |
PubMed
|
|
env
|
A soluble HIV-1 Env trimeric construct may better expose crucial epitopes such as the CD4 binding site and V3, as well as epitopes in the vicinity of gp41, subsequent to conjugation with the synthetic CD4-mimicking mini protein |
PubMed
|
|
env
|
Coexpression of HIV-1 gp160 and human CD4 in HeLa cells severely impairs HIV-1 gp120 production due to the formation of intracellular gp160-CD4 complexes; this CD4-mediated inhibition of gp160 processing is alleviated by coexpression of Vpu |
PubMed
|
|
env
|
Interaction of HIV-1 gp160 with CD4 increases p56lck autophosphorylation and kinase activity |
PubMed
|
|
env
|
ICAM-1 promotes HIV-1 gp160-mediated syncytium formation, and the ICAM-1 contrareceptor LFA-1 attenuates the syncytium-inhibiting activity of virus-neutralizing monoclonal antibodies and soluble CD4 |
PubMed
|
|
env
|
HIV-1 gp160 and gp120 specifically recognize the C-terminal heparin-binding domain of fibronectin (Fn) and this binding inhibits the interaction of gp160/gp120 with soluble CD4 |
PubMed
|
|
env
|
A complete disappearance of surface CD4 preceding single-cell death occurs in cell clones expressing gp160, in which a complex between CD4 and gp160 is formed and then accumulates intracellularly |
PubMed
|
|
env
|
Newly synthesized CD4 and HIV-1 gp160 form a complex prior to transport from the endoplasmic reticulum (ER) |
PubMed
|
|
env
|
Dimeric HIV-1 gp160 binds to two CD4 molecules |
PubMed
|
|
env
|
HIV-1 gp160 alone or CD4/gp160 cross-linking induces tyrosine phosphorylation of intracellular substrates p59fyn, zap 70, and p95vav and also leads to ras activation |
PubMed
|
|
env
|
Amino acid residues 257, 368, 370, and 457 of HIV-1 gp160 are critical for both cell surface and intracellular interaction between gp160 and CD4 |
PubMed
|
|
env
|
Interaction of the anchoring domain of HIV-1 gp160 with the endoplasmic reticulum membrane is responsible for gp160-mediated cell surface downregulation of CD4 |
PubMed
|
|
Envelope transmembrane glycoprotein gp41
|
env
|
Enhanced CD4 binding activity of HIV-1 isolate R3A gp120/gp41 contributes to activate plasmacytoid dendritic cells (pDCs) |
PubMed
|
|
env
|
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
|
|
env
|
Divergent HIV-1 strains differ in their stoichiometry of entry and require between 1 to 7 HIV-1 gp120/gp41 trimers, with most strains depending on 2 to 3 trimers to complete entry through the interaction with CD4 |
PubMed
|
|
env
|
SMS2, but not SMS1, is involved in enhancement of HIV-1 gp120/gp41-mediated membrane fusion through CD4 receptor and CCR5/CXCR4 coreceptors |
PubMed
|
|
env
|
Double alanine mutations at positions 671 and 674 of Env in the gp41 MPER region (residues 662-683) attenuate Env-mediated cell-cell fusion and hemifusion, as well as viral infectivity mediated by both CD4-dependent and -independent viruses |
PubMed
|
|
env
|
CD4 binding to HIV-1 gp120/gp41 trimers results in significant conformational changes in M150 and M161 in gp120 V1/V2 and F316 in gp120 V3, but causes little changes in M104, M95, and the triad of gp41 leucines |
PubMed
|
|
env
|
Shingopeptides disrupt HIV-1 gp41 fusion protein folding and CD4 receptor diffusion in vitro, suggesting that shingopeptides abolish the interaction of gp41 with CD4 in vivo |
PubMed
|
|
env
|
A bivalent HIV-1 inactivator 2DLT by linking the D1D2 domain of CD4 to HIV-1 fusion inhibitor T1144 induces the formation of the gp41 prehairpin fusion-intermediate (PFI) and the T1144 domain in 2DLT then binds to the exposed PFI |
PubMed
|
|
env
|
HIV-1 induces an elongated phenotype in infected CD4+ T cells. These HIV-infected T cells tether to other lymph node CD4+ cells and form syncytia through gp120/gp41, and migrate to distant tissues to disseminate |
PubMed
|
|
env
|
A single Y681H substitution in HIV-1 gp41 increases the gp120-CD4 binding and enhances infectivity in low CD4 expressing cells |
PubMed
|
|
env
|
A truncated cytoplasmic domain of 27 amino acids in HIV-1 gp41 can expose highly conserved domains involved in both HIV-1 coreceptor and CD4 binding |
PubMed
|
|
env
|
Binding gp140 to the synthetic CD4-mimicking mini protein leads to an outward domain shift of the three gp120 subunits, which diminishes gp120-gp41 interactions |
PubMed
|
|
env
|
A point mutation (V38E) in the gp41 region of HIV-1 abolishes HIV-1-mediated apoptosis by CASP3 and minimizes CD4 loss in humanized mice without altering viral replication |
PubMed
|
|
env
|
In resting CD4 T cells, only the HIV envelope-mediated entry, but not the VSV-G-mediated endocytosis, can lead to viral DNA synthesis and nuclear migration |
PubMed
|
|
env
|
The HIV-1 transmembrane glycoprotein gp41 is an amino acceptor and donor substrate for transglutaminase in vitro; soluble CD4 can block the transglutaminase-catalyzed incorporation of the polyamine spermidine into HIV-1 gp41 |
PubMed
|
|
env
|
Virological synapse-mediated cell-to-cell HIV-1 transfer is dependent upon gp120/gp41 and CD4 interactions and is more efficient than that of a cell-free mode of uptake, yet the presence of the full CD4 cytoplasmic tail is not essential for the process |
PubMed
|
|
env
|
Siva-1 sensitizes CD4-positive T-cells to HIV-1 gp120/gp41-induced apoptosis. The Siva-1-mediated sensitization on CD4-positive T-cells shows significant activation of caspase-3, -8, and -9 |
PubMed
|
|
env
|
CIITA-mediated enhancement of HIV-1 infection is gp120/gp41/CD4-dependent and occurs at the early steps in the infection cycle |
PubMed
|
|
env
|
Elimination of the CD4 domain 2 disulfide bond (Cys130-Cys159) by mutation enhances HIV-1 gp120/gp41-mediated cell-cell fusion and virus entry |
PubMed
|
|
Nef
|
nef
|
HIV-1 Nef downregulates CD4 in primary HIV-1 infected CD4+ T cells |
PubMed
|
|
nef
|
HIV-1 NL4-3 Nef downregulates CD4, which requires the CPG-motif in Nef |
PubMed
|
|
nef
|
HIV-1 NL4-3 and SK68 Nef downregulate CD4, which is dependent upon a serine at position 88 in Nef |
PubMed
|
|
nef
|
HIV-1 Nef and Vpu downregulate CD4 in an additive manner, which when inhibited allows for antibodies to bind CD4-Env and drive ADCC |
PubMed
|
|
nef
|
HIV-1 Nef clinical isolates from chronic progressors downregulate CD4 to greater amounts than from elite controllers |
PubMed
|
|
nef
|
HIV-1 NL4-3, Sk68, SF2, and clinical isolates downregulate CD4 surface expression |
PubMed
|
|
nef
|
HIV-1 Nef and Vpu downregulate CD4 expression; Nef and Vpu deletions reverse CD4 downmodulation in an additive fashion |
PubMed
|
|
nef
|
HIV-1 (SF2) Nef downregulates CD4; downregulation is dependent on the dileucine motif in Nef |
PubMed
|
|
nef
|
HIV-1 NA7 Nef downregulates CD4 surface expression; downregulation is dependent upon amino acid D186 in Nef |
PubMed
|
|
nef
|
A dileucine motif in Nef is required for CD4 downregulation and for interaction with clathrin adaptor complexes AP-1 and AP-2, which are responsible for recruiting sorted proteins into clathrin-coated pits |
PubMed
|
|
nef
|
HIV-1 Nef downregulates CD4 molecules from the cell surface of T, B, peripheral blood mononuclear and monocyte/macrophage cell lines as well as non-lymphoid cell lines |
PubMed
|
|
nef
|
HIV-1 Nef core domain directly interacts with CD4 and is highly conserved amongst Nef from [the] HIV-1/-2/SIV strains [tested] in 293T cells as shown by FACS-Forster resonance energy transfer (FRET)- and site-directed mutagenesis-based experiments |
PubMed
|
|
nef
|
HIV-1 (NL4-3) Nef downregulates CD4 via a cullin-RING E3 ubiquitin ligase complex- independent mechanism |
PubMed
|
|
nef
|
HIV-1 isolate R3A Nef mutants G2, WL58, RR106, LL165, E160NNSLL165, and DD175 fail to induce release of IFN-alpha in pDCs, suggesting that the Nef function responsible for CD4 downregulation is crucial for pDCs stimulation by R3A |
PubMed
|
|
nef
|
HIV-1 Nef clones from acute controllers display a lesser ability to downregulate CD4 and HLA class I from the cell surface, and a reduced ability to enhance virion infectivity compared to those from acute progressors |
PubMed
|
|
nef
|
HIV-1 Nef-mediated CD4 degradation requires ALIX and interaction of Nef with ALIX in endosomes containing CD4 in cells |
PubMed
|
|
nef
|
HIV-1 Nef mutants D108K, R134E, E177K, DD174/175AA do not downregulate CD4 on cell surface of HeLa cells |
PubMed
|
|
nef
|
Deletion of both HIV-1 nef and vpu genes enhance a significant engagement between HIV-1 gp120 and CD4 at the cell surface, suggesting Nef and Vpu prevent the exposure of epitopes recognized by anti-gp120 antibody-dependent cell-mediated cytotoxicity |
PubMed
|
|
nef
|
Neffin, a camelid single-domain antibody fragment (termed sdAb19) fused to the SH3 domain of Nef, strongly binds to HIV-1 Nef with a stoichiometric 2:2 ratio and inhibits Nef-mediated downregulation of CD4 in HeLa-CD4 cells |
PubMed
|
|
nef
|
Interaction of HIV-1 Nef with AP-2 alpha-sigma dimer is required for Nef-mediated CD4 downregulation. The dileucine L164L165 and M168L170 motifs bind to the sigma unit, while the acidic motif E174 and D175 binds to the alpha unit |
PubMed
|
|
nef
|
HIV-1 Nef clones, isolated from plasma of elite controllers (EC) and chronic progressors (CP), show significantly lower CD4 downregulation activity in EC than that in CP |
PubMed
|
|
nef
|
HIV-1 Nef clones obtained from chronic patients infected with HIV-1 subtypes A, B, C or D show a functional hierarchy of subtype B > A/D > C for Nef-mediated CD4 downregulation |
PubMed
|
|
nef
|
Functional ARF1 is required for HIV-1 Nef-dependent endogenous HLA-A2 and CD4 downregulation in HIV-infected primary T cells |
PubMed
|
|
nef
|
The hydrophobic region (residues 168-173) downstream of the HIV-1 Nef dileucine motif (L164L165) is involved in HIV-1 Nef-mediated CD4 downregulation |
PubMed
|
|
nef
|
HIV-1 Nef enhances the infectivity of CD4-chemokine receptor-pseudotyped HIV-1 for target cells expressing HIV-1 Env. Virus-producing cells expressing dominant-negative dynamin 2 (K44A) selectively inhibits these receptor-pseudotyped virions |
PubMed
|
|
nef
|
CD4 and MHC-1 downregulation are highly conserved in primary HIV-1 Nef alleles from brain and lymphoid tissues, but Pak2 activation is highly variable |
PubMed
|
|
nef
|
HIV-1 Nef mutants LLAA and delta12-39 significantly impair downregulation of CD4. Nef LLAA mutant fails to interact with the endocytic machinery and Nef delta12-39 mutant lacks the interaction with the Nef-associated kinase complex |
PubMed
|
|
nef
|
HIV-1 Nef drastically reduces the ratio of CD4 dimers/monomers |
PubMed
|
|
nef
|
beta-COP as a cellular cofactor is required for HIV-1 Nef-mediated HLA-A2, CD4, and CD8 downregulation |
PubMed
|
|
nef
|
Single mutation at the ubiquitination residue K144 or at the tyrosine motif Y202F203 in HIV-1 Nef greatly impairs Nef-mediated CD4 downregulation |
PubMed
|
|
nef
|
TPCK and TLCK alkylation reagents chemically modify HIV-1 Nef at residues Cys55 and Cys206. Cys55 modification reduces the strength of the interaction between Nef and CD4 tail peptide |
PubMed
|
|
nef
|
HIV-1 Nef expression from unintegrated HIV-1 DNA downregulates the surface levels of CD4, CCR5, and CXCR4 on T-lymphocytes and monocytes |
PubMed
|
|
nef
|
HIV-1 Nef interacts with CD4 in living cells |
PubMed
|
|
nef
|
HIV-1 Nef targets CD4 to CD63-containing lysosomes for Nef-induced degradation of CD4, which requires the VPS4-mediated ESCRT machinery |
PubMed
|
|
nef
|
K295, K297, K298, and R340 basic residues on the AP-2 alpha subunit are required for its binding to HIV-1 Nef. The K297 and R340 residues are required for Nef-induced CD4 downregulation and the cooperative assembly of a Nef-CD4-AP-2 complex |
PubMed
|
|
nef
|
L37, P78 and E177 residues of HIV-1 Nef are required for its effect on CD4 internalization and recycling but dispensable for Nef-induced retention and degradation of intracellular CD4 |
PubMed
|
|
nef
|
HIV-1 Nef-Vpr fusion proteins are efficiently incorporated into HIV-1 particles and possess CD4 downregulation activity in target cells |
PubMed
|
|
nef
|
An intact Nef dimerization interface, including the multiple hydrophobic (I109, L112, Y115, and F121) and electrostatic (R105 and D123) residues, is required for Nef-induced CD4 downregulation in cells |
PubMed
|
|
nef
|
An intact hydrophobic interface (residues I109, L112, Y115, and F121) is essential for HIV-1 Nef dimerization in cells and is required for Nef-mediated CD4 receptor downregulation |
PubMed
|
|
nef
|
HIV-1 Vpr increases expression of Nef protein from integrase-defective HIV-1. The Vpr-mediated expression of Nef from IN-minus HIV-1 results in CD4 downregulation |
PubMed
|
|
nef
|
Expression of p56(lck) in nonlymphoid CD4-expressing cells restores the ability of Nef in order to increase the internalization rate of CD4 |
PubMed
|
|
nef
|
HIV-1 Nef downregulates CD4 expression on the surface of Jurkat cells and blocks the CD3 signaling pathway; mutations at amino acids 174 and 175 reduce the ability of Nef to downregulate CD4 expression |
PubMed
|
|
nef
|
The HIV-1 Nef mutant F12-HIVNef, containing three rare amino acid substitutions, G(140)E, V(153)L and E(177)G, represses Nef-induced accelerated rates of CD4 internalization and p62NAK activation |
PubMed
|
|
nef
|
Deletion of the 19 N-terminal amino acids, including the myristoylation signal from HIV-1 Nef inhibits both MHC-I and CD4 downregulation while preserving most CTL, T-helper and B-cell epitopes |
PubMed
|
|
nef
|
Different levels of CD4 modulation are induced by different HIV-1 Nef proteins derived from HIV-1 infected adults and children |
PubMed
|
|
nef
|
The functional ability of HIV-1 Nef to downregulate CD4, but not MHC class I, is associated with Nef-mediated enhancement of HIV-1 pathogenicity in severe combined immunodeficiency (SCID) mice implanted with human fetal thymus and liver |
PubMed
|
|
nef
|
CD4 downregulation by HIV-1 Nef enhances the efficiency of HIV-1 replication in both activated human primary T lymphocytes and lymphoid tissues; Nef-induced CD4 downregulation correlates with severe depletion of CD4+ T cells in lymphoid tissues |
PubMed
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nef
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Expression of HIV-1 Nef in human monocyte-derived dendritic cells using an adenovirus based delivery system decreases CD4 levels, but has no effect on class I MHC |
PubMed
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nef
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HIV-1 Nef downregulates CD4 in Jurkat cells in a concentration-dependent manner |
PubMed
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nef
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HIV-1 Nef mutants C142A and K158A/E160G exhibit a temperature-dependent ability to downregulate CD4 |
PubMed
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nef
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HIV-1 Nef downregulates CD4 rapidly during the early phase of virus infection, whereas HIV-1 Vpu and Env function late in the infection; in primary cells, down-modulation of CD4 has a stronger dependence on Nef function for reducing cell surface CD4 |
PubMed
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nef
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High levels of CD4 on the surface of an HIV-1 producing cell block viral infectivity by interfering with incorporation of HIV-1 envelope into the virion; HIV-1 Nef and Vpu inhibit this block by downregulating CD4 from the cell surface |
PubMed
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nef
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Mutational analysis of HIV-1 Nef shows that a membrane targeting domain (residues 2-7) and a conserved glutamic acid-rich segment (residues 60-71) are required for CD4 downregulation but not for viral infectivity enhancement |
PubMed
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nef
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HIV-1 Nef downregulates cell surface expression of CD4 in CEM Nef+ cells by promoting the accumulation of CD4 in an acidic early endosome |
PubMed
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nef
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An isoleucine residue at position 410 and two leucine residues at positions 413 and 414 in CD4 are required for HIV-1 Nef-mediated CD4 downregulation in cells |
PubMed
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nef
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Two distinct regions within HIV-1 Nef, amino acid residues 96-144 and 175-186, are required for CD4 downregulation in cells |
PubMed
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nef
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The presence of an alpha-helix in CD4, which extends from residues Gln403 to Arg406, promotes the binding of CD4 to HIV-1 Nef |
PubMed
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nef
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Yeast two-hybrid assays show that a nearly complete HIV-1 Nef protein is required for binding to the CD4 cytoplasmic domain (residues 394-416), and the dileucine motif in CD4 (residues 413-414) is essential for this direct interaction |
PubMed
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nef
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Solution NMR spectroscopy studies show a 13 amino acid peptide (residues 407-419) derived from the CD4 cytoplasmic domain binds directly to HIV-1 Nef in a manner that involves amino acid residues 57-59, 95-97, 106, and 110 in Nef |
PubMed
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nef
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CEM cells stably transfected with a replication-defective provirus of HIV-1 that has a rev-splicing mutation and expresses an intact nef gene have markedly reduced cell surface expression of CD4 |
PubMed
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nef
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HIV-1 Nef-mediated downregulation of CD4 is induced by an accelerated dissociation of the T-cell tyrosine kinase Lck and CD4, and a decrease in the half-life of CD4 |
PubMed
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nef
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A dileucine motif in the cytoplasmic domain of CD4 is involved in the association of CD4 with the tyrosine kinase Lck and the downregulation of CD4 by HIV-1 Nef, however Nef does not induce dissociation of Lck from CD4 in acutely HIV-infected cells |
PubMed
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nef
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A dileucine motif in the cytoplasmic tail of CD4 is not required for HIV-1 Nef binding in insect cells, but is essential for Nef-induced CD4 downregulation |
PubMed
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nef
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Experiments using both a recombinant HIV-1 Integrase-defective virus and a diketo acid Integrase inhibitor demonstrate that HIV-1 Nef expressed from extra chromosomal DNA (E-DNA) downregulates CD4 surface expression on primary CD4(+) T lymphocytes |
PubMed
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nef
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The Nef protein from the primary virus isolate HIV-1 KS2 lacks two glutamic acid residues (EE154-5) and has a decreased ability to downregulate CD4 |
PubMed
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nef
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HIV-1 expressing Nef proteins defective in CD4 downregulation activity retain wild-type levels of infectivity in single-round assays, but exhibit delayed replication kinetics and lower titers compared to the wild-type virus in monocyte-derived macrophages |
PubMed
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nef
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PMA treatment of T cells expressing HIV-1 Nef, which downregulates CD4, restores cell surface CD4 up to 35%; mutations in the phosphorylation sites of the CD4 cytoplasmic tail (Ser408 and Ser415) abolish this effect of PMA |
PubMed
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nef
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HIV-1 Nef-mediated CD4 downregulation is profoundly inhibited by the synergistic effect of Eps15DIII, a dominant negative mutant of Eps involved in endocytosis and RNA interference of AP-2 expression |
PubMed
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nef
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Bioluminescence resonance energy transfer (BRET) and co-immunoprecipitation assays have been used to demonstrate the interaction of HIV-1 Nef and CD4 in intact human cells |
PubMed
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nef
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HIV-1 group N and group O Nef alleles only weakly downregulate CD4, CD28, and class I and II MHC molecules |
PubMed
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nef
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A dileucine motif in the CD4 cytoplasmic domain is required for its downregulation by HIV-1 Nef; cysteine residues in the cytoplasmic domain of CD4 are essential for the binding of Lck but are not required for Nef-induced downregulation |
PubMed
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nef
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HIV-1 Nef induces drastic and moderate downregulation of CD4 and MHC-I in resting CD4(+) T lymphocytes, respectively, but markedly upregulates cell surface levels of the MHC-II invariant chain CD74 |
PubMed
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nef
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HIV-1 Nef forms a ternary complex with ARF1 and beta-COP in endosomes, which facilitates Nef-induced downregulation and transport of CD4 to acidic late-endosomal compartments |
PubMed
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nef
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HIV-1 Nef-induced CD4 degradation is regulated by a highly conserved diacidic-based motif in Nef that acts as a lysosomal targeting signal through the binding of beta-COP in endosomes |
PubMed
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nef
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Nef from primary isolates of HIV-1 suppresses surface CD4 expression in human and mouse T cells |
PubMed
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nef
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Transduction of the HIV-1 nef gene into murine cells expressing human, chimpanzee, or murine CD4 induces cell surface downregulation of all three molecules; the cytoplasmic domain of CD4 is required for its downregulation by Nef |
PubMed
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nef
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In adult HIV-1 Nef transgenic mice, CD4 downregulation is found in CD4- and CD8-double positive thymocytes; co-localization of CD4 with a Golgi-specific marker indicates Nef interferes with CD4 intracellular trafficking |
PubMed
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nef
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CD4 is downregulated by nef alleles isolated from peripheral blood leukocytes of HIV-1-infected individuals; Nef proteins with point mutations at positions Gly2, Asp36, Cys122, and Val148 exhibit different levels of CD4 downregulation |
PubMed
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nef
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CD4 downregulation by HIV-1 Nef is independent of the level of CD4 mRNA expressed in cells and of the level of CD4 serine phosphorylation |
PubMed
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nef
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Overexpression of Nef-associated factor 1, Naf1, increases cell surface CD4 expression; HIV-1 Nef suppresses this activity of Naf1 to downregulate CD4 expression |
PubMed
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Pr55(Gag)
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gag
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HIV-1 Gag colocalizes with CD4 on bystander cells in virological synapses in Cos7 cells |
PubMed
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gag
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HIV-1 Gag/p24 co-localizes with CD4 in the intracellular CD4+ compartments in primary T lymphocytes |
PubMed
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gag
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The rapid kinetics of HIV-1 Gag transfer corresponds to similar time-dependent increases in CD4+ T cell infection from HIV-1 infected monocyte-derived macrophages |
PubMed
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gag
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HIV-1 Gag-positive uropods form contacts enriched in CD4 |
PubMed
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Tat
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tat
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HIV-1 Tat-induced upregulation of miR-222 results in the post-transcriptional inhibition of CD4 expression |
PubMed
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tat
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CD4 and CD1a surface expression are greatly decreased in Tat expression Jurkat cells |
PubMed
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tat
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Expression of HRES-1/Rab4 is induced by HIV-1 tat, which in turn down-regulates expression of CD4 and susceptibility to re-infection by HIV-1 |
PubMed
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tat
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HIV-1 Tat upregulates mRNA expression and cell surface levels of CD4 antigen in Jurkat cells |
PubMed
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Vif
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vif
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Vif plays an important role in promoting HIV-1 binding to CD4 |
PubMed
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Vpr
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vpr
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HIV-1 Nef-Vpr fusion proteins are efficiently incorporated into HIV-1 particles and possess CD4 downregulation activity in target cells |
PubMed
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vpr
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HIV-1 Vpr increases expression of Nef protein from integrase-defective HIV-1. The Vpr-mediated expression of Nef from IN-minus HIV-1 results in CD4 downregulation |
PubMed
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vpr
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HIV-1 Vpr downregulates the expression of surface CD4 receptors in Jurkat T cells |
PubMed
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Vpu
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vpu
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HIV-1 Nef and Vpu downregulate CD4 in an additive manner, which when inhibited allows for antibodies to bind CD4-Env and drive ADCC |
PubMed
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vpu
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HIV-1 Nef and Vpu downregulate CD4 expression; Nef and Vpu deletions reverse CD4 downmodulation in an additive fashion |
PubMed
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vpu
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HIV-1 (NL4-3) Vpu downregulates CD4; downregulation is dependent on the presence of serines at positions 52 and 56 in Vpu |
PubMed
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vpu
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The C-terminal domain of HIV-1 Vpu (amino acids 76-81) interacts with the cytoplasmic domain of CD4 (amino acids 402-425) and causes the rapid degradation of CD4 in the endoplasmic reticulum |
PubMed
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vpu
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Downregulation of CD4 from the surface of HIV-1 infected cells by HIV-1 Vpu increases viral infectivity |
PubMed
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vpu
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HIV-1 Vpu downregulates cell (CEMT4, Primary CD4+ T cells) surface expression of CD4 |
PubMed
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vpu
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HIV-1 Vpu downregulates CD4 and is dependent on neddylation (covalent addition of NEDD8 onto a lysine residue on cullin backbone inducing conformational change in the cullin-RING E3 ubiquitin ligase complex rendering enzyme catalytically active) via NAE1 |
PubMed
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vpu
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HIV-1 Vpu mediates retention of CD4 in the ER. Transmembrane domain interactions are the main determinant of ER retention of CD4 by Vpu |
PubMed
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vpu
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Poly-ubiquitination of the CD4 cytosolic tail by SCFbeta-TrCP is required for HIV-1 Vpu-induced CD4 degradation |
PubMed
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vpu
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HIV-1 Vpu mediated degradation of CD4 requires the function of proteasomes and results from the formation of a ternary complex between beta-TrCP, Vpu and CD4 which connects CD4 to the endoplasmic reticulum degradation pathway |
PubMed
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vpu
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Deletion of both HIV-1 nef and vpu genes enhance a significant engagement between HIV-1 gp120 and CD4 at the cell surface, suggesting Nef and Vpu prevent the exposure of epitopes recognized by anti-gp120 antibody-dependent cell-mediated cytotoxicity |
PubMed
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vpu
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Biotinylation technique in living cells demonstrates HIV-1 Vpu-induced retro-translocation of CD4 travels with oxidized intrachain disulfide bridges and accumulates in the cytosol as reduced and deglycosylated molecules only upon proteasomal inhibition |
PubMed
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vpu
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HIV-1 Vpu mutations (A19E, E29K, II43,46SL, R49G/T, SN53,55RH, S53N, E58K) derived from HIV-1 infected patients have defects for both CD4 and tetherin downregulation |
PubMed
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vpu
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Individual Vpu proteins isolated from chronically or acutely infected patients differ substantially in their CD4 and tetherin downregulation function at the cell surface |
PubMed
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vpu
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HIV-1 Vpu interacts with CD4 in living cells |
PubMed
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vpu
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Cell surface CD4 inhibits HIV-1 particle release by interfering with Vpu activity, possibly by disrupting the oligomeric structure of Vpu |
PubMed
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vpu
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HIV-1 Vpu regulates the formation of intracellular HIV-1 gp160-CD4 complexes and liberates Golgi-targeted gp160 from CD4-dependent retention in the endoplasmic reticulum |
PubMed
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vpu
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Chimeras between the TMD of HIV-1 M Vpu and the cytoplasmic domains of SIVcpzPtt, SIVcpzPts, and SIVgor Vpu proteins are capable of binding to human CD4 |
PubMed
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vpu
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A combination of molecular dynamics simulations and docking approaches shows the lowest energy structure of Vpu-CD4, indicating that the residues Leu-419 and Ile-416 in CD4 interact with the alanine rim (Ala-8/11/15/19) of Vpu |
PubMed
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vpu
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Magic angle sample spinning NMR analysis confirms the correct insertion of the transmembrane domains from both HIV-1 Vpu and CD4 (residues 372-433) into the lipid bilayers |
PubMed
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vpu
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The Val20 and Ser23 residues within the Vpu TMD are critical for Vpu-induced CD4 retention in the ER |
PubMed
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vpu
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Mutation of the HIV-1 Vpu Trp22 does not prevent Vpu-CD4 interaction but enhances Vpu oligomerization. The CD4 Gly415 residue within the CD4 TMD is required for both Vpu-CD4 interaction and Vpu-induced CD4 degradation |
PubMed
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vpu
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The HIV-1 Vpu Trp22 mutation in the Vpu transmembrane domain fails to induce CD4 degradation by reduced CD4 polyubiquitination. The Trp residue is highly conserved in all HIV-1 Vpu variants, including those of HIV-1 groups M, N, and O |
PubMed
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vpu
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NMR analysis indicates that amino acids (residues 39-48 and 64-70) in both helices of the HIV-1 Vpu cytoplasmic region are important for its binding to CD4 |
PubMed
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vpu
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Tetherin delGPI mutant directly interacts with HIV-1 Vpu and inhibits Vpu-induced degradation of tetherin and CD4 |
PubMed
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vpu
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The putative cholesterol recognition amino acid consensus (CRAC) motif (residues 25-31) of HIV-1 Vpu mediates lipid raft association of Vpu and affects the downregulation of cell surface CD4 |
PubMed
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vpu
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HIV-1 Vpu from subtype P can downregulate CD4 from cell surface |
PubMed
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vpu
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Downregulation of CD4 and BST2 by HIV-1 Vpu is observed in HIV-1 infected humanized mice |
PubMed
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vpu
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SCYL2 inhibits Vpu-induced BST2 and CD4 reduction at the cell surface by suppressing the phosphorylation of Vpu at positions Ser-52 and Ser-56 |
PubMed
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vpu
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Co-expression of HIV-1 Vpu with beta-TrCP2 induces degradation of total cellular CD4 content; Vpu-mediated CD4 down-modulation is inhibited by double silencing of beta-TrCP1 and beta-TrCP2 |
PubMed
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vpu
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The invariant leucine 63 and the valine 68 within the predicted second alpha-helical domain of the HIV-1 Vpu cytoplasmic tail are required for CD4 down-modulation. L63A and V68A mutants still bind CD4 and retain the ability to interact with beta-TrCP1 |
PubMed
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vpu
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Replication-defective Vpu TM mutants (V9D and I19D) and cytoplasmic domain mutants (S56G and E59K) fail to downregulate cell surface CD4, suggesting that viral replication potential and ability to downregulate CD4 by Vpu are correlated |
PubMed
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vpu
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HIV-1 Vpu Y35A/L39G mutant has a significant increase in CD4 surface expression compared to wild-type Vpu |
PubMed
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vpu
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HIV-1 Vpu proteins from pandemic HIV-1 M strains, but not from nonpandemic HIV-1 N strains, degrade the viral receptor CD4 |
PubMed
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vpu
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The VCP-UFD1L-NPL4 complex is required for HIV-1 Vpu-induced CD4 degradation in the ER-associated degradation pathway. The ATPase activity of VCP and ubiquitin binding to UFD1L are important for CD4 degradation by Vpu |
PubMed
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vpu
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A simian-human immunodeficiency virus (SHIVtm) with a scrambled amino acid sequence in the transmembrane domain of HIV-1 Vpu fails to downregulate cell surface expression of CD4 |
PubMed
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vpu
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Phosphorylation of HIV-1 Vpu on two serine phosphoacceptor sites (amino acids 52 and 56) by casein kinase 2 is required for Vpu-mediated degradation of CD4 in the endoplasmic reticulum |
PubMed
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