Gene Symbol: CD4
Description: CD4 molecule
Alias: CD4mut, T-cell surface glycoprotein CD4, CD4 antigen (p55), CD4 receptor, T-cell surface antigen T4/Leu-3
Species: human
Products:     CD4

Top Publications

  1. Leonard J, Filzen T, Carter C, Schaefer M, Collins K. HIV-1 Nef disrupts intracellular trafficking of major histocompatibility complex class I, CD4, CD8, and CD28 by distinct pathways that share common elements. J Virol. 2011;85:6867-81 pubmed publisher
    ..The best-characterized targets of Nef are major histocompatibility complex class I (MHC-I) and CD4, but Nef also has been reported to target several other proteins, including CD8β, CD28, CD80, CD86, and CD1d...
  2. Zhou T, Georgiev I, Wu X, Yang Z, Dai K, Finzi A, et al. Structural basis for broad and potent neutralization of HIV-1 by antibody VRC01. Science. 2010;329:811-7 pubmed publisher
    ..HIV-1 infection, antibodies are generated against the region of the viral gp120 envelope glycoprotein that binds CD4, the primary receptor for HIV-1...
  3. Wu X, Yang Z, Li Y, Hogerkorp C, Schief W, Seaman M, et al. Rational design of envelope identifies broadly neutralizing human monoclonal antibodies to HIV-1. Science. 2010;329:856-61 pubmed publisher develop antigenically resurfaced glycoproteins specific for the structurally conserved site of initial CD4 receptor binding...
  4. Llewellyn G, Hogue I, Grover J, Ono A. Nucleocapsid promotes localization of HIV-1 gag to uropods that participate in virological synapses between T cells. PLoS Pathog. 2010;6:e1001167 pubmed publisher
    ..Cell contacts enriched in Gag and CD4, which define the virological synapse (VS), are also enriched in uropod markers...
  5. Agrawal Gamse C, Lee F, Haggarty B, Jordan A, Yi Y, Lee B, et al. Adaptive mutations in a human immunodeficiency virus type 1 envelope protein with a truncated V3 loop restore function by improving interactions with CD4. J Virol. 2009;83:11005-15 pubmed publisher
    ..The adapted virus, termed TA1, retained the V3 truncation, was exquisitely sensitive to neutralization by the CD4 binding site monoclonal antibody b12 and by HIV-positive human sera, used CCR5 to enter cells, and was completely ..
  6. Finzi A, Xiang S, Pacheco B, Wang L, Haight J, Kassa A, et al. Topological layers in the HIV-1 gp120 inner domain regulate gp41 interaction and CD4-triggered conformational transitions. Mol Cell. 2010;37:656-67 pubmed publisher
    ..virus (HIV-1) into cells is initiated by binding of the gp120 exterior envelope glycoprotein to the receptor, CD4. How does CD4 binding trigger conformational changes in gp120 that allow the gp41 transmembrane envelope ..
  7. Chen L, Kwon Y, Zhou T, Wu X, O Dell S, Cavacini L, et al. Structural basis of immune evasion at the site of CD4 attachment on HIV-1 gp120. Science. 2009;326:1123-7 pubmed publisher
    The site on HIV-1 gp120 that binds to the CD4 receptor is vulnerable to antibodies. However, most antibodies that interact with this site cannot neutralize HIV-1...
  8. Mulampaka S, Dixit N. Estimating the threshold surface density of Gp120-CCR5 complexes necessary for HIV-1 envelope-mediated cell-cell fusion. PLoS ONE. 2011;6:e19941 pubmed publisher
    Reduced expression of CCR5 on target CD4(+) cells lowers their susceptibility to infection by R5-tropic HIV-1, potentially preventing transmission of infection and delaying disease progression...
  9. Sierra Aragón S, Walter H. Targets for inhibition of HIV replication: entry, enzyme action, release and maturation. Intervirology. 2012;55:84-97 pubmed publisher
    ..Additional targets will have to be defined to achieve the ultimate goal: the eradication of the virus from the infected human body. ..

More Information

Publications129 found, 100 shown here

  1. Guttman M, Kahn M, Garcia N, Hu S, Lee K. Solution structure, conformational dynamics, and CD4-induced activation in full-length, glycosylated, monomeric HIV gp120. J Virol. 2012;86:8750-64 pubmed publisher
    ..Here we investigate full-length, glycosylated HIV gp120 in unliganded and CD4-bound forms by using small-angle X-ray scattering to visualize global structural reorganization and hydrogen/..
  2. Julien J, Cupo A, Sok D, Stanfield R, Lyumkis D, Deller M, et al. Crystal structure of a soluble cleaved HIV-1 envelope trimer. Science. 2013;342:1477-83 pubmed publisher
    HIV-1 entry into CD4(+) target cells is mediated by cleaved envelope glycoprotein (Env) trimers that have been challenging to characterize structurally. Here, we describe the crystal structure at 4...
  3. Doria Rose N, Georgiev I, O Dell S, Chuang G, Staupe R, McLellan J, et al. A short segment of the HIV-1 gp120 V1/V2 region is a major determinant of resistance to V1/V2 neutralizing antibodies. J Virol. 2012;86:8319-23 pubmed publisher
  4. Tran E, Borgnia M, Kuybeda O, Schauder D, Bartesaghi A, Frank G, et al. Structural mechanism of trimeric HIV-1 envelope glycoprotein activation. PLoS Pathog. 2012;8:e1002797 pubmed publisher
    HIV-1 infection begins with the binding of trimeric viral envelope glycoproteins (Env) to CD4 and a co-receptor on target T-cells...
  5. Doria M. Role of the CD4 down-modulation activity of Nef in HIV-1 infectivity. Curr HIV Res. 2011;9:490-5 pubmed
    ..Some findings indicate that the CD4 down-regulation activity of Nef is critical for viral infectivity as well as for progression to immunodeficiency...
  6. Zou W, Denton P, Watkins R, Krisko J, Nochi T, Foster J, et al. Nef functions in BLT mice to enhance HIV-1 replication and deplete CD4+CD8+ thymocytes. Retrovirology. 2012;9:44 pubmed publisher
    ..8,200,000?±?1,800,000 copies of viral RNA/ml, range 3,600,000 to 20,400,000; n?=?9) and exhaustively depletes CD4+ T cells in blood and tissues...
  7. Götz N, Sauter D, Usmani S, Fritz J, Goffinet C, Heigele A, et al. Reacquisition of Nef-mediated tetherin antagonism in a single in vivo passage of HIV-1 through its original chimpanzee host. Cell Host Microbe. 2012;12:373-80 pubmed publisher
    ..Our data demonstrate that primate lentiviruses can reacquire lost accessory gene functions during a single in vivo passage and suggest that other functional constraints keep Nef ready to regain antitetherin activity...
  8. Sigal A, Kim J, Balazs A, Dekel E, Mayo A, Milo R, et al. Cell-to-cell spread of HIV permits ongoing replication despite antiretroviral therapy. Nature. 2011;477:95-8 pubmed publisher
  9. François K, Balzarini J. The highly conserved glycan at asparagine 260 of HIV-1 gp120 is indispensable for viral entry. J Biol Chem. 2011;286:42900-10 pubmed publisher
    ..We observed a significant lower CD4 binding in the case of the N260Q mutant gp120 virus strains, caused by a strikingly lower expression of gp120 and ..
  10. Chikere K, Chou T, Gorry P, Lee B. Affinofile profiling: how efficiency of CD4/CCR5 usage impacts the biological and pathogenic phenotype of HIV. Virology. 2013;435:81-91 pubmed publisher
    HIV-1 envelope (Env) uses CD4 and a coreceptor (CCR5 and/or CXCR4) for viral entry. The efficiency of receptor/coreceptor mediated entry has important implications for HIV pathogenesis and transmission...
  11. Dey A, Burke B, Sun Y, Sirokman K, Nandi A, Hartog K, et al. Elicitation of neutralizing antibodies directed against CD4-induced epitope(s) using a CD4 mimetic cross-linked to a HIV-1 envelope glycoprotein. PLoS ONE. 2012;7:e30233 pubmed publisher
    ..Here, we focus on a structure that stabilizes Env in a conformation representative of its primary (CD4) receptor-bound state, thereby exposing highly conserved "CD4 induced" (CD4i) epitope(s) known to be ..
  12. Cimbro R, Gallant T, Dolan M, Guzzo C, Zhang P, Lin Y, et al. Tyrosine sulfation in the second variable loop (V2) of HIV-1 gp120 stabilizes V2-V3 interaction and modulates neutralization sensitivity. Proc Natl Acad Sci U S A. 2014;111:3152-7 pubmed publisher
    ..region of the second variable loop (V2) of gp120 contains sulfated tyrosines (Tys173 and Tys177) that in the CD4-unbound prefusion state mediate intramolecular interaction between V2 and the conserved base of the third variable ..
  13. Watkins J, Diaz Rodriguez J, Siddappa N, Corti D, Ruprecht R. Efficiency of neutralizing antibodies targeting the CD4-binding site: influence of conformational masking by the V2 loop in R5-tropic clade C simian-human immunodeficiency virus. J Virol. 2011;85:12811-4 pubmed publisher
    ..3N) deletion mutation in the V2 loop stem of gp120 as the major determinant of neutralization escape of the anti-CD4-binding site (anti-CD4-bs) neutralizing monoclonal antibody (nMAb) b12...
  14. West A, Diskin R, Nussenzweig M, Bjorkman P. Structural basis for germ-line gene usage of a potent class of antibodies targeting the CD4-binding site of HIV-1 gp120. Proc Natl Acad Sci U S A. 2012;109:E2083-90 pubmed publisher
    A large number of anti-HIV-1 antibodies targeting the CD4-binding site (CD4bs) on the envelope glycoprotein gp120 have recently been reported. These antibodies, typified by VRC01, are remarkable for both their breadth and their potency...
  15. Klein F, Gaebler C, Mouquet H, Sather D, Lehmann C, Scheid J, et al. Broad neutralization by a combination of antibodies recognizing the CD4 binding site and a new conformational epitope on the HIV-1 envelope protein. J Exp Med. 2012;209:1469-79 pubmed publisher
    ..method identified antibodies that bind to a new broadly neutralizing epitope in the vicinity of the V3 loop and the CD4-induced site (CD4i)...
  16. Mwimanzi P, Markle T, Martin E, Ogata Y, Kuang X, Tokunaga M, et al. Attenuation of multiple Nef functions in HIV-1 elite controllers. Retrovirology. 2013;10:1 pubmed publisher
    ..of 91 Nef clones, isolated from plasma of 45 EC and 46 chronic progressors (CP), to down-regulate HLA class I and CD4, up-regulate HLA class II invariant chain (CD74), enhance viral infectivity, and stimulate viral replication in PBMC...
  17. White T, Bartesaghi A, Borgnia M, de la Cruz M, Nandwani R, Hoxie J, et al. Three-dimensional structures of soluble CD4-bound states of trimeric simian immunodeficiency virus envelope glycoproteins determined by using cryo-electron tomography. J Virol. 2011;85:12114-23 pubmed publisher
    ..Although binding of gp120 to cell surface CD4 and a chemokine receptor is known to elicit conformational changes in gp120 and gp41, changes in quaternary ..
  18. Schnur E, Noah E, Ayzenshtat I, Sargsyan H, Inui T, Ding F, et al. The conformation and orientation of a 27-residue CCR5 peptide in a ternary complex with HIV-1 gp120 and a CD4-mimic peptide. J Mol Biol. 2011;410:778-97 pubmed publisher
    Interaction of CC chemokine receptor 5 (CCR5) with the human immunodeficiency virus type 1 (HIV-1) gp120/CD4 complex involves its amino-terminal domain (Nt-CCR5) and requires sulfation of two to four tyrosine residues in Nt-CCR5...
  19. McLellan J, Pancera M, Carrico C, Gorman J, Julien J, Khayat R, et al. Structure of HIV-1 gp120 V1/V2 domain with broadly neutralizing antibody PG9. Nature. 2011;480:336-43 pubmed publisher
    ..In addition to structurally defining V1/V2, the results thus identify a paradigm of antibody recognition for highly glycosylated antigens, which-with PG9-involves a site of vulnerability comprising just two glycans and a strand. ..
  20. Guan Y, Pazgier M, Sajadi M, Kamin Lewis R, Al Darmarki S, Flinko R, et al. Diverse specificity and effector function among human antibodies to HIV-1 envelope glycoprotein epitopes exposed by CD4 binding. Proc Natl Acad Sci U S A. 2013;110:E69-78 pubmed publisher
    The HIV-1 envelope glycoprotein (Env) undergoes conformational transitions consequent to CD4 binding and coreceptor engagement during viral entry...
  21. Lucas T, Janaka S, Stephens E, Johnson M. Vpu downmodulates two distinct targets, tetherin and gibbon ape leukemia virus envelope, through shared features in the Vpu cytoplasmic tail. PLoS ONE. 2012;7:e51741 pubmed publisher
    During human immunodeficiency virus-1 (HIV-1) assembly, the host proteins CD4 (the HIV-1 receptor) and tetherin (an interferon stimulated anti-viral protein) both reduce viral fitness...
  22. Jardine J, Julien J, Menis S, Ota T, Kalyuzhniy O, McGuire A, et al. Rational HIV immunogen design to target specific germline B cell receptors. Science. 2013;340:711-6 pubmed publisher
    ..Potent VRC01-class bNAbs against the CD4 binding site of HIV gp120 have been isolated from HIV-1-infected individuals; however, such bNAbs have not been ..
  23. Harris A, Borgnia M, Shi D, Bartesaghi A, He H, Pejchal R, et al. Trimeric HIV-1 glycoprotein gp140 immunogens and native HIV-1 envelope glycoproteins display the same closed and open quaternary molecular architectures. Proc Natl Acad Sci U S A. 2011;108:11440-5 pubmed publisher
    The initial step in HIV-1 infection occurs with the binding of cell surface CD4 to trimeric HIV-1 envelope glycoproteins (Env), a heterodimer of a transmembrane glycoprotein (gp41) and a surface glycoprotein (gp120)...
  24. Jolly C, Welsch S, Michor S, Sattentau Q. The regulated secretory pathway in CD4(+) T cells contributes to human immunodeficiency virus type-1 cell-to-cell spread at the virological synapse. PLoS Pathog. 2011;7:e1002226 pubmed publisher
    ..Immunodeficiency Virus type-1 (HIV-1) at the virological synapse (VS) is an efficient mode of dissemination between CD4(+) T cells but the mechanisms by which HIV-1 proteins are directed towards intercellular contacts is unclear...
  25. Kwon Y, Finzi A, Wu X, Dogo Isonagie C, Lee L, Moore L, et al. Unliganded HIV-1 gp120 core structures assume the CD4-bound conformation with regulation by quaternary interactions and variable loops. Proc Natl Acad Sci U S A. 2012;109:5663-8 pubmed publisher
    ..Engagement of CD4, the primary human receptor, fixes a particular conformation and primes Env for entry...
  26. Wibmer C, Bhiman J, Gray E, Tumba N, Abdool Karim S, Williamson C, et al. Viral escape from HIV-1 neutralizing antibodies drives increased plasma neutralization breadth through sequential recognition of multiple epitopes and immunotypes. PLoS Pathog. 2013;9:e1003738 pubmed publisher
    ..neutralizing V2 antibodies through deletion of the glycan at N160 was associated with exposure of an epitope in the CD4 binding site that became the target for a second wave of broadly neutralizing antibodies...
  27. Vermeire J, Vanbillemont G, Witkowski W, Verhasselt B. The Nef-infectivity enigma: mechanisms of enhanced lentiviral infection. Curr HIV Res. 2011;9:474-89 pubmed
    ..Hereby we aim to contribute to a better understanding of this highly conserved and therapeutically attractive Nef function. ..
  28. Klasse P. The molecular basis of HIV entry. Cell Microbiol. 2012;14:1183-92 pubmed publisher
    ..The key players in this entry by fusion are the envelope glycoprotein, on the viral side, and CD4 and a co-receptor, CCR5 or CXCR4, on the cellular side...
  29. Yang X, Jiao Y, Wang R, Ji Y, Zhang H, Zhang Y, et al. High CCR5 density on central memory CD4+ T cells in acute HIV-1 infection is mostly associated with rapid disease progression. PLoS ONE. 2012;7:e49526 pubmed publisher
    b>CD4+ central memory T cells play a critical role in the pathogenesis of simian immunodeficiency virus disease, and the CCR5 density on the surface of CD4 T cells is an important factor in human immunodeficiency virus (HIV)-1 disease ..
  30. Gorry P, Francella N, Lewin S, Collman R. HIV-1 envelope-receptor interactions required for macrophage infection and implications for current HIV-1 cure strategies. J Leukoc Biol. 2014;95:71-81 pubmed publisher
    ..mechanisms underlying HIV-1 tropism for macrophages are complex, involving enhanced and/or altered interactions with CD4, CCR5, and/or CXCR4, and that the nature of these interactions may depend on the anatomical location of the virus.
  31. Mikell I, Stamatatos L. Evolution of cross-neutralizing antibody specificities to the CD4-BS and the carbohydrate cloak of the HIV Env in an HIV-1-infected subject. PLoS ONE. 2012;7:e49610 pubmed publisher
    ..The first specificity became evident at 3 years post infection and targeted the CD4-binding site of Env...
  32. Mwimanzi P, Markle T, Ueno T, Brockman M. Human leukocyte antigen (HLA) class I down-regulation by human immunodeficiency virus type 1 negative factor (HIV-1 Nef): what might we learn from natural sequence variants?. Viruses. 2012;4:1711-30 pubmed publisher
    HIV-1 causes a chronic infection in humans that is characterized by high plasma viremia, progressive loss of CD4+ T lymphocytes, and severe immunodeficiency resulting in opportunistic disease and AIDS...
  33. García Expósito L, Ziglio S, Barroso González J, de Armas Rillo L, Valera M, Zipeto D, et al. Gelsolin activity controls efficient early HIV-1 infection. Retrovirology. 2013;10:39 pubmed publisher
    ..These alterations are necessary for the redistribution of CD4-CXCR4/CCR5 to one pole of the cell, a process that increases the probability of HIV-1 Envelope (Env)-CD4/co-..
  34. Magadán J, Bonifacino J. Transmembrane domain determinants of CD4 Downregulation by HIV-1 Vpu. J Virol. 2012;86:757-72 pubmed publisher
    ..The downregulation of the CD4 coreceptor by the Vpu protein of HIV-1 is a prime example of a process that is dependent on specific properties of ..
  35. Duncan C, Williams J, Schiffner T, Gärtner K, Ochsenbauer C, Kappes J, et al. High-multiplicity HIV-1 infection and neutralizing antibody evasion mediated by the macrophage-T cell virological synapse. J Virol. 2014;88:2025-34 pubmed publisher that monocyte-derived macrophages (MDM) efficiently transmit a high-multiplicity HIV-1 infection to autologous CD4(+) T cells through a viral envelope glycoprotein (Env) receptor- and actin-dependent virological synapse (VS), ..
  36. Amorim N, da Silva E, de Castro R, da Silva Januário M, Mendonça L, Bonifacino J, et al. Interaction of HIV-1 Nef protein with the host protein Alix promotes lysosomal targeting of CD4 receptor. J Biol Chem. 2014;289:27744-56 pubmed publisher
    ..A key function of Nef is the down-regulation of the coreceptor CD4 from the surface of the host cells...
  37. Heigele A, Schindler M, Gnanadurai C, Leonard J, Collins K, Kirchhoff F. Down-modulation of CD8αβ is a fundamental activity of primate lentiviral Nef proteins. J Virol. 2012;86:36-48 pubmed publisher
    ..for the interaction of HIV-1 Nef with AP-2, and they were also shown to be critical for down-modulation of CD4 and CD28, but not MHC-I, by SIV Nefs...
  38. Duenas Decamp M, O Connell O, Corti D, Zolla Pazner S, Clapham P. The W100 pocket on HIV-1 gp120 penetrated by b12 is not a target for other CD4bs monoclonal antibodies. Retrovirology. 2012;9:9 pubmed publisher
    The conserved CD4 binding site (CD4bs) on HIV-1 gp120 is a major target for vaccines. It is a priority to determine sites and structures within the CD4bs that are important for inclusion in vaccines...
  39. Kovacs J, Nkolola J, Peng H, Cheung A, Perry J, Miller C, et al. HIV-1 envelope trimer elicits more potent neutralizing antibody responses than monomeric gp120. Proc Natl Acad Sci U S A. 2012;109:12111-6 pubmed publisher
    ..These results, which demonstrate that there are relevant immunologic differences between monomers and high-quality envelope trimers, have important implications for HIV-1 vaccine development. ..
  40. Jin Y, Cai C, Mezei M, Ohlmeyer M, Sanchez R, Burakoff S. Identification of a novel binding site between HIV type 1 Nef C-terminal flexible loop and AP2 required for Nef-mediated CD4 downregulation. AIDS Res Hum Retroviruses. 2013;29:725-31 pubmed publisher
    ..Nef promotes viral replication and infection by connecting CD4 and several other cell surface receptors to the clathrin adaptor protein AP2, resulting in the internalization and ..
  41. Shen R, Meng G, Ochsenbauer C, Clapham P, Grams J, Novak L, et al. Stromal down-regulation of macrophage CD4/CCR5 expression and NF-?B activation mediates HIV-1 non-permissiveness in intestinal macrophages. PLoS Pathog. 2011;7:e1002060 pubmed publisher
    ..Exposure of monocytes to S-CM blocked up-regulation of CD4 and CCR5 expression during monocyte differentiation into macrophages and inhibited productive HIV-1 infection in ..
  42. Sato K, Misawa N, Fukuhara M, Iwami S, An D, Ito M, et al. Vpu augments the initial burst phase of HIV-1 propagation and downregulates BST2 and CD4 in humanized mice. J Virol. 2012;86:5000-13 pubmed publisher
    ..Vpu also possesses the ability to downmodulate cellular CD4 and SLAMF6 molecules expressed on infected cells...
  43. Wu X, Wang C, O Dell S, Li Y, Keele B, Yang Z, et al. Selection pressure on HIV-1 envelope by broadly neutralizing antibodies to the conserved CD4-binding site. J Virol. 2012;86:5844-56 pubmed publisher
    ..progressing HIV-1-infected donor and was shown to neutralize diverse HIV-1 strains by binding to the conserved CD4 binding site (CD4bs) of gp120...
  44. Mwimanzi P, Markle T, Ogata Y, Martin E, Tokunaga M, Mahiti M, et al. Dynamic range of Nef functions in chronic HIV-1 infection. Virology. 2013;439:74-80 pubmed publisher
    ..Relative to a control Nef from HIV-1 strain SF2, HLA class I and CD4 down-regulation activities of 46 plasma RNA Nef sequences derived from unique chronic infected individuals were ..
  45. Acharya P, Luongo T, Georgiev I, Matz J, Schmidt S, Louder M, et al. Heavy chain-only IgG2b llama antibody effects near-pan HIV-1 neutralization by recognizing a CD4-induced epitope that includes elements of coreceptor- and CD4-binding sites. J Virol. 2013;87:10173-81 pubmed publisher
    ..The crystal structure at 2.1-Å resolution of VHH JM4 bound to HIV-1 YU2 gp120 stabilized in the CD4-bound state by the CD4-mimetic miniprotein, M48U1, revealed a JM4 epitope that combined regions of coreceptor ..
  46. Zhuang K, Finzi A, Tasca S, Shakirzyanova M, Knight H, Westmoreland S, et al. Adoption of an "open" envelope conformation facilitating CD4 binding and structural remodeling precedes coreceptor switch in R5 SHIV-infected macaques. PLoS ONE. 2011;6:e21350 pubmed publisher
    ..of tropism switch is the adoption of a less constrained and more "open" envelope conformation for better CD4 usage, allowing greater structural flexibility to accommodate further mutational changes that confer CXCR4 ..
  47. Matusali G, Potestà M, Santoni A, Cerboni C, Doria M. The human immunodeficiency virus type 1 Nef and Vpu proteins downregulate the natural killer cell-activating ligand PVR. J Virol. 2012;86:4496-504 pubmed publisher
  48. Parrish N, Wilen C, Banks L, Iyer S, Pfaff J, Salazar Gonzalez J, et al. Transmitted/founder and chronic subtype C HIV-1 use CD4 and CCR5 receptors with equal efficiency and are not inhibited by blocking the integrin ?4?7. PLoS Pathog. 2012;8:e1002686 pubmed publisher
    ..We found that T/F and chronic control Envs were indistinguishable in the efficiency with which they used CD4 and CCR5...
  49. Demirkhanyan L, Marin M, Padilla Parra S, Zhan C, Miyauchi K, Jean Baptiste M, et al. Multifaceted mechanisms of HIV-1 entry inhibition by human ?-defensin. J Biol Chem. 2012;287:28821-38 pubmed publisher
    ..found that, surprisingly, this ?-defensin inhibited multiple steps of virus entry, including: (i) Env binding to CD4 and coreceptors; (ii) refolding of Env into the final 6-helix bundle structure; and (iii) productive HIV-1 uptake ..
  50. Salimi H, Roche M, Webb N, Gray L, Chikere K, Sterjovski J, et al. Macrophage-tropic HIV-1 variants from brain demonstrate alterations in the way gp120 engages both CD4 and CCR5. J Leukoc Biol. 2013;93:113-26 pubmed publisher
    ..methods and mathematical modeling to generate quantitative VERSA metrics that simultaneously measure Env-CD4 and Env-CCR5 interactions...
  51. Morellato Castillo L, Acharya P, Combes O, Michiels J, Descours A, Ramos O, et al. Interfacial cavity filling to optimize CD4-mimetic miniprotein interactions with HIV-1 surface glycoprotein. J Med Chem. 2013;56:5033-47 pubmed publisher
    ..A hollow (Phe43 cavity) between HIV-1 surface glycoprotein (gp120) and cluster of differentiation 4 (CD4) receptor extends beyond residue phenylalanine 43 of CD4 and cannot be fully accessed by natural amino acids...
  52. Murooka T, Deruaz M, Marangoni F, Vrbanac V, Seung E, von Andrian U, et al. HIV-infected T cells are migratory vehicles for viral dissemination. Nature. 2012;490:283-7 pubmed publisher
    ..Both uncoordinated motility of syncytia and adhesion to CD4(+) lymph node cells led to the formation of long membrane tethers, increasing cell lengths to up to ten times that ..
  53. McGee K, Haim H, Korioth Schmitz B, Espy N, Javanbakht H, Letvin N, et al. The selection of low envelope glycoprotein reactivity to soluble CD4 and cold during simian-human immunodeficiency virus infection of rhesus macaques. J Virol. 2014;88:21-40 pubmed publisher
    ..conformation from the metastable unliganded state in response to the binding of ligands (antibodies and soluble CD4 [sCD4]) or incubation in the cold...
  54. Liu Y, SchOn A, Freire E. Optimization of CD4/gp120 inhibitors by thermodynamic-guided alanine-scanning mutagenesis. Chem Biol Drug Des. 2013;81:72-8 pubmed publisher
    ..We demonstrate the approach by developing the combined binding and allosteric hotspots blueprint for CD4/gp120, the initial interaction leading to HIV-1 cell infection...
  55. Lyumkis D, Julien J, de Val N, Cupo A, Potter C, Klasse P, et al. Cryo-EM structure of a fully glycosylated soluble cleaved HIV-1 envelope trimer. Science. 2013;342:1484-90 pubmed publisher
    ..664 gp140) in complex with a CD4 binding site (CD4bs) bnAb, PGV04, at 5.8 angstrom resolution...
  56. Zuo J, Suen J, Wong A, Lewis M, Ayub A, Belzer M, et al. Functional analysis of HIV type 1 Nef gene variants from adolescent and adult survivors of perinatal infection. AIDS Res Hum Retroviruses. 2012;28:486-92 pubmed publisher
    ..into an HIV-derived vector that permits simultaneous evaluation of the impact of the Nef protein on MHC-I and CD4 cell surface expression...
  57. Ghiglione Y, Turk G. Nef performance in macrophages: the master orchestrator of viral persistence and spread. Curr HIV Res. 2011;9:505-13 pubmed
    ..Here, we will review the newest findings describing how monocytes/macrophages natural pathways are altered by Nef protein, highlighting how viral and host biology are perturbed in consequence. ..
  58. Meyerson J, Tran E, Kuybeda O, Chen W, Dimitrov D, Gorlani A, et al. Molecular structures of trimeric HIV-1 Env in complex with small antibody derivatives. Proc Natl Acad Sci U S A. 2013;110:513-8 pubmed publisher
    ..HIV-1 BaL virions complexed separately to two small (~15 kDa) HIV-neutralizing proteins: A12, which binds the CD4-binding site on Env, and m36, whose binding to Env is enhanced by CD4 binding...
  59. Engelman A, Cherepanov P. The structural biology of HIV-1: mechanistic and therapeutic insights. Nat Rev Microbiol. 2012;10:279-90 pubmed publisher
    ..Here, we review recent advances in HIV-1 structural biology, focusing on the molecular mechanisms of viral replication and on the development of new therapeutics. ..
  60. Lv M, Wang J, Wang X, Zuo T, Zhu Y, Kong W, et al. Polarity changes in the transmembrane domain core of HIV-1 Vpu inhibits its anti-tetherin activity. PLoS ONE. 2011;6:e20890 pubmed publisher
    ..had similar subcellular localization patterns with that of wild-type Vpu and were functional with respect to CD4 downregulation. We showed that the hydrophobic binding surface for tetherin lies in the core of the Vpu TM domain...
  61. Walker L, Huber M, Doores K, Falkowska E, Pejchal R, Julien J, et al. Broad neutralization coverage of HIV by multiple highly potent antibodies. Nature. 2011;477:466-70 pubmed publisher
  62. Ringe R, Sharma D, Zolla Pazner S, Phogat S, Risbud A, Thakar M, et al. A single amino acid substitution in the C4 region in gp120 confers enhanced neutralization of HIV-1 by modulating CD4 binding sites and V3 loop. Virology. 2011;418:123-32 pubmed publisher
    ..Substitution of I424M in unrelated Envs also showed similar neutralization phenotype, indicating that M424 in C4 region induces exposure of neutralizing epitopes particularly in CD4 binding sites and V3 loop.
  63. Arrildt K, Joseph S, Swanstrom R. The HIV-1 env protein: a coat of many colors. Curr HIV/AIDS Rep. 2012;9:52-63 pubmed publisher
    ..CD4+ T cells due to viral entry requirements for the CCR5 coreceptor and for high surface levels of the CD4 receptor. This is the case for the transmitted virus and for most of the virus sampled in the blood...
  64. Singh S, Möckel L, Thiagarajan Rosenkranz P, Wittlich M, Willbold D, Koenig B. Mapping the interaction between the cytoplasmic domains of HIV-1 viral protein U and human CD4 with NMR spectroscopy. FEBS J. 2012;279:3705-3714 pubmed publisher
    Viral protein U (VpU) of HIV-1 plays an important role in downregulation of the main HIV-1 receptor CD4 from the surface of infected cells...
  65. Tuzer F, Madani N, Kamanna K, Zentner I, LaLonde J, Holmes A, et al. HIV-1 Env gp120 structural determinants for peptide triazole dual receptor site antagonism. Proteins. 2013;81:271-90 pubmed publisher
    ..viral spike and inhibit its interaction with both of its cell surface protein ligands, namely the initial receptor CD4 and the co-receptor (CCR5/CXCR4), thus preventing viral entry...
  66. Blumenthal R, Durell S, Viard M. HIV entry and envelope glycoprotein-mediated fusion. J Biol Chem. 2012;287:40841-9 pubmed publisher
    ..However, the coupling between the lipid and protein pathways that give rise to fusion has not been resolved. Here, we discuss the known and unknown about the overall HIV Env-mediated fusion process. ..
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    ..Finally, several Env-stabilizing substitutions could stabilize Env spikes from HIV-1 clades A, B and C. Spike stabilizing mutations may be useful in the development of Env immunogens that stably retain native, trimeric structure. ..
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    ..MAbs against CD4-induced (CD4i) epitopes considered hidden on functional envelope structures poorly bound these viruses and were not ..
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    ..we investigated the mechanism of exposure of these epitopes and found that envelope interaction with the HIV-1 CD4 receptor is required to expose some of these epitopes...
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    The Nef protein of HIV-1 downregulates the cell surface co-receptor CD4 by hijacking the clathrin adaptor complex AP-2. The structural basis for the hijacking of AP-2 by Nef is revealed by a 2...
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    ..of four target sites: (i) SH3 domain interaction, (ii) interference with protein transport processes, (iii) CD4 binding and (iv) targeting to lipid membranes...
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    ..on the HIV envelope glycoprotein, gp120, and demonstrate extreme dependence on the formation of a gp120-human CD4 receptor complex...
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    ..This review will focus on the mechanisms through which the HIV-1 accessory proteins modulate their respective ligands, and its implication for NK cell killing of HIV-infected cells. ..
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    ..Target cells express the HIV-1 receptors, CD4 and CCR5, and carry the firefly luciferase (F-Luc) reporter gene under the control of a tTA-responsive promoter...
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    ..On average, nef alleles from both groups were equally active in modulating CD4, TCR-CD3, CD28, MHC-I, and Ii cell surface expression and in enhancing virion infectivity...
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    ..Molecular characterizations of the antibodies and, most importantly, of the sites of vulnerability that they recognize give hope for the discovery of new vaccines and drugs. ..
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    ..Together, these structural and biophysical findings should facilitate the design of HIV-1 immunogens that possess all elements of the quaternary PG9 epitope required to induce broadly neutralizing antibodies against this region. ..
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    ..Moreover, the gp140 monomers respond to CD4 binding in manner that is consistent with the initial stages of Env activation: CD4 binding induces structural ..
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    ..Our findings strongly encourage the investigation of monoclonal antibody therapy for HIV-1 in humans. ..
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    ..These data provide important insights relevant to HIV-1 vaccine development. ..
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    ..The site includes portions of gp41 and N-linked glycans adjacent to the CD4-binding site on gp120, making 8ANC195 the first donor-derived anti-HIV-1 bNAb with an epitope spanning both Env ..
  84. Wonderlich E, Leonard J, Kulpa D, Leopold K, Norman J, Collins K. ADP ribosylation factor 1 activity is required to recruit AP-1 to the major histocompatibility complex class I (MHC-I) cytoplasmic tail and disrupt MHC-I trafficking in HIV-1-infected primary T cells. J Virol. 2011;85:12216-26 pubmed publisher
    ..These data support a model in which Nef and ARF-1 stabilize an interaction between MHC-I and AP-1 to disrupt the presentation of HIV-1 epitopes to CTLs. ..
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    Antibodies against the CD4 binding site (CD4bs) on the HIV-1 spike protein gp120 can show exceptional potency and breadth. We determined structures of NIH45-46, a more potent clonal variant of VRC01, alone and bound to gp120...
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    ..In addition, the design of a single domain antibody from llama that interferes with CD4 down-regulation activity and PAK2 binding is discussed...
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    ..For entry to occur gp120 sequentially engages the host protein CD4 and then one of two chemokine coreceptors, either CCR5 or CXCR4...
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    Binding of the viral envelope protein (Env), and particularly of its gp120 subunit, to the cellular CD4 receptor is the first essential step of the HIV-1 entry process...
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    Broadly neutralizing antibodies to the CD4 binding site (CD4bs) of gp120 are generated by some HIV-1-infected individuals, but little is known about the prevalence and evolution of this antibody response during the course of HIV-1 ..
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    ..HIV-1 entry by specific bilateral interaction both with the viral envelope and with its primary cellular receptor, CD4. Despite low amino acid identity, human defensin-5 (HD5) shares with HNPs a high degree of structural homology...
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    ..b>CD4 engagement with the gp120 exterior envelope glycoprotein subunit represents the first step during HIV-1 entry...
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    ..despite these adaptive changes, most N-Vpus still antagonize human tetherin only poorly and fail to down-modulate CD4, the natural killer (NK) cell ligand NTB-A as well as the lipid-antigen presenting protein CD1d...