nef

Summary

Gene Symbol: nef
Description: p27
Alias: p27, Nef
Species: Human immunodeficiency virus 1
Products:     nef

Top Publications

  1. Schaefer M, Wonderlich E, Roeth J, Leonard J, Collins K. HIV-1 Nef targets MHC-I and CD4 for degradation via a final common beta-COP-dependent pathway in T cells. PLoS Pathog. 2008;4:e1000131 pubmed publisher
    To facilitate viral infection and spread, HIV-1 Nef disrupts the surface expression of the viral receptor (CD4) and molecules capable of presenting HIV antigens to the immune system (MHC-I)...
  2. Lenassi M, Cagney G, Liao M, Vaupotic T, Bartholomeeusen K, Cheng Y, et al. HIV Nef is secreted in exosomes and triggers apoptosis in bystander CD4+ T cells. Traffic. 2010;11:110-22 pubmed publisher
    The HIV accessory protein negative factor (Nef) is one of the earliest and most abundantly expressed viral proteins. It is also found in the serum of infected individuals (Caby MP, Lankar D, Vincendeau-Scherrer C, Raposo G, Bonnerot C...
  3. Gerlach H, Laumann V, Martens S, Becker C, Goody R, Geyer M. HIV-1 Nef membrane association depends on charge, curvature, composition and sequence. Nat Chem Biol. 2010;6:46-53 pubmed publisher
    b>Nef-mediated internalization of T-cell receptor molecules from the surface of an infected cell is required for the pathogenicity of HIV and disease progression to AIDS...
  4. Stolp B, Abraham L, Rudolph J, Fackler O. Lentiviral Nef proteins utilize PAK2-mediated deregulation of cofilin as a general strategy to interfere with actin remodeling. J Virol. 2010;84:3935-48 pubmed publisher
    b>Nef is an accessory protein and pathogenicity factor of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) which elevates virus replication in vivo...
  5. Mwimanzi P, Hasan Z, Tokunaga M, Gatanaga H, Oka S, Ueno T. Naturally arising HIV-1 Nef variants conferring escape from cytotoxic T lymphocytes influence viral entry co-receptor expression and susceptibility to superinfection. Biochem Biophys Res Commun. 2010;403:422-7 pubmed publisher
    HIV-1 Nef is a key factor for pathogenesis and is known to down-regulate functionally important molecules, including viral entry co-receptor CCR5 and CXCR4, from the surface of HIV-infected cells...
  6. Jung J, Byeon I, Ahn J, Gronenborn A. Structure, dynamics, and Hck interaction of full-length HIV-1 Nef. Proteins. 2011;79:1609-22 pubmed publisher
    b>Nef is an HIV accessory protein that plays an important role in the progression of disease after viral infection. It interferes with numerous signaling pathways, one of which involves serine/threonine kinases...
  7. Singh R, Lau D, Noviello C, Ghosh P, Guatelli J. An MHC-I cytoplasmic domain/HIV-1 Nef fusion protein binds directly to the mu subunit of the AP-1 endosomal coat complex. PLoS ONE. 2009;4:e8364 pubmed publisher
    ..The down-regulation of the major histocompatibility complex class I (MHC-I) from the surface of infected cells by the Nef proteins of primate immunodeficiency viruses likely contributes to pathogenesis by providing evasion of cell-..
  8. Sarmady M, Dampier W, Tozeren A. Sequence- and interactome-based prediction of viral protein hotspots targeting host proteins: a case study for HIV Nef. PLoS ONE. 2011;6:e20735 pubmed publisher
    ..Our results match experimental data on binding sites of Nef to host proteins such as MAPK1, VAV1, LCK, HCK, HLA-A, CD4, FYN, and GNB2L1 with high statistical significance but ..
  9. Trible R, Emert Sedlak L, Wales T, Ayyavoo V, Engen J, Smithgall T. Allosteric loss-of-function mutations in HIV-1 Nef from a long-term non-progressor. J Mol Biol. 2007;374:121-9 pubmed
    Activation of Src family kinases by human immunodeficiency virus type 1 (HIV-1) Nef may play an important role in the pathogenesis of HIV/AIDS...
  10. 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
    ..Viral persistence is mediated in part by the ability of the Nef protein to down-regulate HLA molecules on the infected cell surface, thereby allowing HIV-1 to evade recognition by ..

Detail Information

Publications103 found, 100 shown here

  1. Schaefer M, Wonderlich E, Roeth J, Leonard J, Collins K. HIV-1 Nef targets MHC-I and CD4 for degradation via a final common beta-COP-dependent pathway in T cells. PLoS Pathog. 2008;4:e1000131 pubmed publisher
    To facilitate viral infection and spread, HIV-1 Nef disrupts the surface expression of the viral receptor (CD4) and molecules capable of presenting HIV antigens to the immune system (MHC-I)...
  2. Lenassi M, Cagney G, Liao M, Vaupotic T, Bartholomeeusen K, Cheng Y, et al. HIV Nef is secreted in exosomes and triggers apoptosis in bystander CD4+ T cells. Traffic. 2010;11:110-22 pubmed publisher
    The HIV accessory protein negative factor (Nef) is one of the earliest and most abundantly expressed viral proteins. It is also found in the serum of infected individuals (Caby MP, Lankar D, Vincendeau-Scherrer C, Raposo G, Bonnerot C...
  3. Gerlach H, Laumann V, Martens S, Becker C, Goody R, Geyer M. HIV-1 Nef membrane association depends on charge, curvature, composition and sequence. Nat Chem Biol. 2010;6:46-53 pubmed publisher
    b>Nef-mediated internalization of T-cell receptor molecules from the surface of an infected cell is required for the pathogenicity of HIV and disease progression to AIDS...
  4. Stolp B, Abraham L, Rudolph J, Fackler O. Lentiviral Nef proteins utilize PAK2-mediated deregulation of cofilin as a general strategy to interfere with actin remodeling. J Virol. 2010;84:3935-48 pubmed publisher
    b>Nef is an accessory protein and pathogenicity factor of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) which elevates virus replication in vivo...
  5. Mwimanzi P, Hasan Z, Tokunaga M, Gatanaga H, Oka S, Ueno T. Naturally arising HIV-1 Nef variants conferring escape from cytotoxic T lymphocytes influence viral entry co-receptor expression and susceptibility to superinfection. Biochem Biophys Res Commun. 2010;403:422-7 pubmed publisher
    HIV-1 Nef is a key factor for pathogenesis and is known to down-regulate functionally important molecules, including viral entry co-receptor CCR5 and CXCR4, from the surface of HIV-infected cells...
  6. Jung J, Byeon I, Ahn J, Gronenborn A. Structure, dynamics, and Hck interaction of full-length HIV-1 Nef. Proteins. 2011;79:1609-22 pubmed publisher
    b>Nef is an HIV accessory protein that plays an important role in the progression of disease after viral infection. It interferes with numerous signaling pathways, one of which involves serine/threonine kinases...
  7. Singh R, Lau D, Noviello C, Ghosh P, Guatelli J. An MHC-I cytoplasmic domain/HIV-1 Nef fusion protein binds directly to the mu subunit of the AP-1 endosomal coat complex. PLoS ONE. 2009;4:e8364 pubmed publisher
    ..The down-regulation of the major histocompatibility complex class I (MHC-I) from the surface of infected cells by the Nef proteins of primate immunodeficiency viruses likely contributes to pathogenesis by providing evasion of cell-..
  8. Sarmady M, Dampier W, Tozeren A. Sequence- and interactome-based prediction of viral protein hotspots targeting host proteins: a case study for HIV Nef. PLoS ONE. 2011;6:e20735 pubmed publisher
    ..Our results match experimental data on binding sites of Nef to host proteins such as MAPK1, VAV1, LCK, HCK, HLA-A, CD4, FYN, and GNB2L1 with high statistical significance but ..
  9. Trible R, Emert Sedlak L, Wales T, Ayyavoo V, Engen J, Smithgall T. Allosteric loss-of-function mutations in HIV-1 Nef from a long-term non-progressor. J Mol Biol. 2007;374:121-9 pubmed
    Activation of Src family kinases by human immunodeficiency virus type 1 (HIV-1) Nef may play an important role in the pathogenesis of HIV/AIDS...
  10. 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
    ..Viral persistence is mediated in part by the ability of the Nef protein to down-regulate HLA molecules on the infected cell surface, thereby allowing HIV-1 to evade recognition by ..
  11. Pizzato M, Helander A, Popova E, Calistri A, Zamborlini A, Palu G, et al. Dynamin 2 is required for the enhancement of HIV-1 infectivity by Nef. Proc Natl Acad Sci U S A. 2007;104:6812-7 pubmed
    b>Nef is a virulence factor of HIV-1 and other primate lentiviruses that is crucial for rapid progression to AIDS. In cell culture, Nef increases the infectivity of HIV-1 progeny virions by an unknown mechanism...
  12. Lubben N, Sahlender D, Motley A, Lehner P, Benaroch P, Robinson M. HIV-1 Nef-induced down-regulation of MHC class I requires AP-1 and clathrin but not PACS-1 and is impeded by AP-2. Mol Biol Cell. 2007;18:3351-65 pubmed
    ..complex class I is down-regulated from the surface of human immunodeficiency virus (HIV)-1-infected cells by Nef, a virally encoded protein that is thought to reroute MHC-I to the trans-Golgi network (TGN) in a phosphofurin ..
  13. Turk G, Gundlach S, Carobene M, Schindler M, Salomon H, Benaroch P. Single Nef proteins from HIV type 1 subtypes C and F fail to upregulate invariant chain cell surface expression but are active for other functions. AIDS Res Hum Retroviruses. 2009;25:285-96 pubmed publisher
    HIV-1 Nef protein plays a major role in viral immunopathogenesis, modulating surface expression of several immune receptors, altering signal transduction pathways, and enhancing viral infectivity, among other activities...
  14. Morgan C, Miglionico B, Engen J. Effects of HIV-1 Nef on human N-myristoyltransferase 1. Biochemistry. 2011;50:3394-403 pubmed publisher
    The HIV-1 accessory protein Nef is N-terminally myristoylated, and this post-translational modification is essential for Nef function in AIDS progression...
  15. Munch J, Rajan D, Schindler M, Specht A, Rücker E, Novembre F, et al. Nef-mediated enhancement of virion infectivity and stimulation of viral replication are fundamental properties of primate lentiviruses. J Virol. 2007;81:13852-64 pubmed
    b>Nef is a multifunctional accessory protein of primate lentiviruses...
  16. Iijima S, Lee Y, Ode H, Arold S, Kimura N, Yokoyama M, et al. A noncanonical mu-1A-binding motif in the N terminus of HIV-1 Nef determines its ability to downregulate major histocompatibility complex class I in T lymphocytes. J Virol. 2012;86:3944-51 pubmed publisher
    Downregulation of major histocompatibility complex class I (MHC-I) by HIV-1 Nef protein is indispensable for evasion of protective immunity by HIV-1...
  17. Meuwissen P, Stolp B, Iannucci V, Vermeire J, Naessens E, Saksela K, et al. Identification of a highly conserved valine-glycine-phenylalanine amino acid triplet required for HIV-1 Nef function. Retrovirology. 2012;9:34 pubmed publisher
    The Nef protein of HIV facilitates virus replication and disease progression in infected patients...
  18. Drakesmith H, Chen N, Ledermann H, Screaton G, Townsend A, Xu X. HIV-1 Nef down-regulates the hemochromatosis protein HFE, manipulating cellular iron homeostasis. Proc Natl Acad Sci U S A. 2005;102:11017-22 pubmed
    The multifunctional Nef protein of HIV-1 is important for the progression to AIDS. One action of Nef is to down-regulate surface MHC I molecules, helping infected cells to evade immunity...
  19. Tachado S, Zhang J, Zhu J, Patel N, Koziel H. HIV impairs TNF-alpha release in response to Toll-like receptor 4 stimulation in human macrophages in vitro. Am J Respir Cell Mol Biol. 2005;33:610-21 pubmed
    ..HIV nef protein was sufficient to reduce TNF-alpha release and induce MKP-1 in healthy macrophages...
  20. Cerboni C, Neri F, Casartelli N, Zingoni A, Cosman D, Rossi P, et al. Human immunodeficiency virus 1 Nef protein downmodulates the ligands of the activating receptor NKG2D and inhibits natural killer cell-mediated cytotoxicity. J Gen Virol. 2007;88:242-50 pubmed
    ..Results show that the HIV-1 Nef protein downmodulates cell-surface expression of MICA, ULBP1 and ULBP2, with a stronger effect on the latter ..
  21. Laforge M, Petit F, Estaquier J, Senik A. Commitment to apoptosis in CD4(+) T lymphocytes productively infected with human immunodeficiency virus type 1 is initiated by lysosomal membrane permeabilization, itself induced by the isolated expression of the viral protein Nef. J Virol. 2007;81:11426-40 pubmed
    ..The transfection of activated CD4(+) T lymphocytes with a Nef expression vector rapidly induced the permeabilization of lysosomes and the release of Cat-D, with these two events ..
  22. Noviello C, Benichou S, Guatelli J. Cooperative binding of the class I major histocompatibility complex cytoplasmic domain and human immunodeficiency virus type 1 Nef to the endosomal AP-1 complex via its mu subunit. J Virol. 2008;82:1249-58 pubmed
    Human immunodeficiency virus type 1 Nef provides immune evasion by decreasing the expression of major histocompatibility complex class I (MHC-I) at the surfaces of infected cells...
  23. Emert Sedlak L, Kodama T, Lerner E, Dai W, Foster C, Day B, et al. Chemical library screens targeting an HIV-1 accessory factor/host cell kinase complex identify novel antiretroviral compounds. ACS Chem Biol. 2009;4:939-47 pubmed publisher
    b>Nef is an HIV-1 accessory protein essential for AIDS progression and an attractive target for drug discovery. Lack of a catalytic function makes Nef difficult to assay in chemical library screens...
  24. Laguette N, Benichou S, Basmaciogullari S. Human immunodeficiency virus type 1 Nef incorporation into virions does not increase infectivity. J Virol. 2009;83:1093-104 pubmed publisher
    The viral protein Nef contributes to the optimal infectivity of human and simian immunodeficiency viruses. The requirement for Nef during viral biogenesis particles suggests that Nef might play a role in this process...
  25. Stolp B, Reichman Fried M, Abraham L, Pan X, Giese S, Hannemann S, et al. HIV-1 Nef interferes with host cell motility by deregulation of Cofilin. Cell Host Microbe. 2009;6:174-86 pubmed publisher
    HIV-1 Nef is a key factor in AIDS pathogenesis. Here, we report that Nef potently inhibits motility of fibroblasts and chemotaxis of HIV-1-infected primary human T lymphocytes toward the chemokines SDF-1alpha, CCL-19, and CCL-21 ex vivo...
  26. Lamers S, Salemi M, Galligan D, Morris A, Gray R, FOGEL G, et al. Human immunodeficiency virus-1 evolutionary patterns associated with pathogenic processes in the brain. J Neurovirol. 2010;16:230-41 pubmed publisher
    ..HIV-1 DNA was also amplified from multiple tissues of two HAD patients. Analysis of HIV-1 nef, gp120, and gp41 sequences showed reduced viral evolution within brain tissues for the non-HAD cases relative to ..
  27. Mangino G, Percario Z, Fiorucci G, Vaccari G, Acconcia F, Chiarabelli C, et al. HIV-1 Nef induces proinflammatory state in macrophages through its acidic cluster domain: involvement of TNF alpha receptor associated factor 2. PLoS ONE. 2011;6:e22982 pubmed publisher
    HIV-1 Nef is a virulence factor that plays multiple roles during HIV replication...
  28. Haller C, Rauch S, Michel N, Hannemann S, Lehmann M, Keppler O, et al. The HIV-1 pathogenicity factor Nef interferes with maturation of stimulatory T-lymphocyte contacts by modulation of N-Wasp activity. J Biol Chem. 2006;281:19618-30 pubmed
    The Nef protein is a key determinant of human immunodeficiency virus (HIV) pathogenicity that, among other activities, sensitizes T-lymphocytes for optimal virus production...
  29. Wildum S, Schindler M, Munch J, Kirchhoff F. Contribution of Vpu, Env, and Nef to CD4 down-modulation and resistance of human immunodeficiency virus type 1-infected T cells to superinfection. J Virol. 2006;80:8047-59 pubmed
    Human immunodeficiency virus type 1 (HIV-1) utilizes Vpu, Env, and Nef to down-modulate its primary CD4 receptor from the cell surface, and this function seems to be critical for the pathogenesis of AIDS...
  30. Chen D, Balamurugan A, Ng H, Cumberland W, Yang O. Epitope targeting and viral inoculum are determinants of Nef-mediated immune evasion of HIV-1 from cytotoxic T lymphocytes. Blood. 2012;120:100-11 pubmed publisher
    The impact of HIV-1 Nef-mediated HLA-I down-regulation on CD8(+) cytotoxic T lymphocytes (CTLs) varies by epitope, but the determining factors have not been elucidated...
  31. 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
    ..EC) who spontaneously suppress plasma viremia to < 50 RNA copies/mL; however, activity of the accessory protein Nef remains incompletely characterized...
  32. 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
    HIV-1 Nef is required for efficient viral replication and pathogenesis...
  33. Acheampong E, Parveen Z, Muthoga L, Kalayeh M, Mukhtar M, Pomerantz R. Human Immunodeficiency virus type 1 Nef potently induces apoptosis in primary human brain microvascular endothelial cells via the activation of caspases. J Virol. 2005;79:4257-69 pubmed
    The lentiviral protein Nef plays a major role in the pathogenesis of human immunodeficiency virus type I (HIV-1) infection...
  34. 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 Nef protein is an important HIV virulence factor that promotes the degradation of host proteins to augment virus production and facilitate immune evasion...
  35. Saksela K. Interactions of the HIV/SIV pathogenicity factor Nef with SH3 domain-containing host cell proteins. Curr HIV Res. 2011;9:531-42 pubmed
    A bewildering number of host cell proteins associated with Nef can be found in the literature and in the public protein interaction databases...
  36. Li P, Wang T, Buckley K, Chenine A, Popov S, Ruprecht R. Phosphorylation of HIV Nef by cAMP-dependent protein kinase. Virology. 2005;331:367-74 pubmed
    b>Nef, a multifunctional accessory protein of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV), is important for disease progression...
  37. Yan Q, Ma X, Shen C, Cao X, Feng N, Qin D, et al. Inhibition of Kaposi's sarcoma-associated herpesvirus lytic replication by HIV-1 Nef and cellular microRNA hsa-miR-1258. J Virol. 2014;88:4987-5000 pubmed publisher
    ..We have previously shown that negative factor (Nef), a secreted HIV-1 protein, synergizes with KSHV viral interleukin-6 (vIL-6) to promote angiogenesis and ..
  38. Schindler M, Rajan D, Specht A, Ritter C, Pulkkinen K, Saksela K, et al. Association of Nef with p21-activated kinase 2 is dispensable for efficient human immunodeficiency virus type 1 replication and cytopathicity in ex vivo-infected human lymphoid tissue. J Virol. 2007;81:13005-14 pubmed
    Interaction of the human immunodeficiency virus type 1 (HIV-1) Nef protein with p21-activated kinase 2 (PAK2) has been proposed to play a role in T-cell activation, viral replication, apoptosis, and progression to AIDS...
  39. Kirchhoff F, Schindler M, Specht A, Arhel N, Munch J. Role of Nef in primate lentiviral immunopathogenesis. Cell Mol Life Sci. 2008;65:2621-36 pubmed publisher
    More than a decade ago it was established that intact nef genes are critical for efficient viral persistence and greatly accelerate disease progression in SIVmac-infected rhesus macaques and in HIV-1-infected humans...
  40. Chaudhuri R, Mattera R, Lindwasser O, Robinson M, Bonifacino J. A basic patch on alpha-adaptin is required for binding of human immunodeficiency virus type 1 Nef and cooperative assembly of a CD4-Nef-AP-2 complex. J Virol. 2009;83:2518-30 pubmed publisher
    A critical function of the human immunodeficiency virus type 1 Nef protein is the downregulation of CD4 from the surfaces of infected cells...
  41. Rawat P, Mitra D. Cellular heat shock factor 1 positively regulates human immunodeficiency virus-1 gene expression and replication by two distinct pathways. Nucleic Acids Res. 2011;39:5879-92 pubmed publisher
    ..We have reported earlier Nef-dependent induction of HSP40 leading to increased HIV-1 gene expression; however, the mechanism of induction ..
  42. Quaranta M, Falzano L, Vincentini O, Fiorentini C, Giordani L, Viora M. Effects of HIV-1 Nef on virus co-receptor expression and cytokine release in human bladder, laryngeal, and intestinal epithelial cell lines. Viral Immunol. 2011;24:245-50 pubmed publisher
    ..In the present study, we analyzed the effect of the accessory HIV-1 Nef protein on mucosal EC, using unstimulated or IFN-?-stimulated HEp-2, T24, and Caco2?cell lines as models for ..
  43. Mukerji J, Olivieri K, Misra V, Agopian K, Gabuzda D. Proteomic analysis of HIV-1 Nef cellular binding partners reveals a role for exocyst complex proteins in mediating enhancement of intercellular nanotube formation. Retrovirology. 2012;9:33 pubmed publisher
    HIV-1 Nef protein contributes to pathogenesis via multiple functions that include enhancement of viral replication and infectivity, alteration of intracellular trafficking, and modulation of cellular signaling pathways...
  44. Fenard D, Yonemoto W, de Noronha C, Cavrois M, Williams S, Greene W. Nef is physically recruited into the immunological synapse and potentiates T cell activation early after TCR engagement. J Immunol. 2005;175:6050-7 pubmed
    The HIV-1 protein Nef enhances viral pathogenicity and accelerates disease progression in vivo. Nef potentiates T cell activation by an unknown mechanism, probably by optimizing the intracellular environment for HIV replication...
  45. Pugliese A, Vidotto V, Beltramo T, Torre D. Regulation of interleukin-18 by THP-1 monocytoid cells stimulated with HIV-1 and Nef viral protein. Eur Cytokine Netw. 2005;16:186-90 pubmed
    ..001). Of the following viral proteins: gp 120, p24 and Nef, only the last one induced decreased IL-18 secretion in the supernatants of THP-1 cells...
  46. Ariën K, Verhasselt B. HIV Nef: role in pathogenesis and viral fitness. Curr HIV Res. 2008;6:200-8 pubmed
    Conserved in all primate lentivirus genomes, Nef promotes viral replication and infectivity, influences the trafficking of a large number of surface receptors and interferes with TCR signalling, consequently modulating T-cell activation...
  47. Horenkamp F, Breuer S, Schulte A, Lülf S, Weyand M, Saksela K, et al. Conformation of the dileucine-based sorting motif in HIV-1 Nef revealed by intermolecular domain assembly. Traffic. 2011;12:867-77 pubmed publisher
    The human immunodeficiency virus 1 (HIV-1) Nef protein is a pathogenicity factor required for effective progression to AIDS, which modulates host cell signaling pathways and T-cell receptor internalization...
  48. Brown A, Gartner S, Kawano T, Benoit N, Cheng Mayer C. HLA-A2 down-regulation on primary human macrophages infected with an M-tropic EGFP-tagged HIV-1 reporter virus. J Leukoc Biol. 2005;78:675-85 pubmed
    ..The 27-kD Nef protein has been shown to down-modulate specific genes of the major histocompatibility complex class I (MHC-I) on ..
  49. Lu T, He J, Wang Z, Feng X, Fukumi Tominaga T, Chen N, et al. HIV-1 Nef disrupts the podocyte actin cytoskeleton by interacting with diaphanous interacting protein. J Biol Chem. 2008;283:8173-82 pubmed publisher
    The ability of the human immunodeficiency virus, type 1 (HIV-1) protein Nef to induce cytoskeleton changes in infected host cells is a key event in viral replication...
  50. Quaranta M, Mattioli B, Giordani L, Viora M. Immunoregulatory effects of HIV-1 Nef protein. Biofactors. 2009;35:169-74 pubmed publisher
    ..HIV-1 codes for proteins, including the accessory Nef proteins, that interacting with immune cells may contribute to AIDS pathogenesis...
  51. Chaudhry A, Verghese D, Das S, Jameel S, George A, Bal V, et al. HIV-1 Nef promotes endocytosis of cell surface MHC class II molecules via a constitutive pathway. J Immunol. 2009;183:2415-24 pubmed publisher
    HIV-1 Nef has been reported to disrupt MHC class II (MHCII)-mediated Ag presentation by a dual strategy that comprises a reduction in cell surface levels of peptide-loaded mature MHCII molecules and a up-regulation of immature MHCII ..
  52. Yi L, Rosales T, Rose J, Chowdhury B, Chaudhury B, Knutson J, et al. HIV-1 Nef binds a subpopulation of MHC-I throughout its trafficking itinerary and down-regulates MHC-I by perturbing both anterograde and retrograde trafficking. J Biol Chem. 2010;285:30884-905 pubmed publisher
    The HIV protein Nef is thought to mediate immune evasion and promote viral persistence in part by down-regulating major histocompatibility complex class I protein (MHC-I or HLA-I) from the cell surface...
  53. Abraham L, Fackler O. HIV-1 Nef: a multifaceted modulator of T cell receptor signaling. Cell Commun Signal. 2012;10:39 pubmed publisher
    b>Nef, an accessory protein of the Human Immunodeficiency Virus type 1 (HIV-1), is dispensable for viral replication in cell culture, but promotes virus replication and pathogenesis in the infected host...
  54. Bentham M, Mazaleyrat S, Harris M. Role of myristoylation and N-terminal basic residues in membrane association of the human immunodeficiency virus type 1 Nef protein. J Gen Virol. 2006;87:563-71 pubmed
    Human immunodeficiency virus type 1 Nef protein is N-terminally myristoylated, a modification reported to be required for the association of Nef with cytoplasmic membranes...
  55. Laguette N, Br gnard C, Benichou S, Basmaciogullari S. Human immunodeficiency virus (HIV) type-1, HIV-2 and simian immunodeficiency virus Nef proteins. Mol Aspects Med. 2010;31:418-33 pubmed publisher
    ..Human and simian lentiviruses have acquired non-structural proteins among which Nef plays a major role in the evolution of viral infection towards an immunodeficiency syndrome...
  56. Schmökel J, Sauter D, Schindler M, Leendertz F, Bailes E, Dazza M, et al. The presence of a vpu gene and the lack of Nef-mediated downmodulation of T cell receptor-CD3 are not always linked in primate lentiviruses. J Virol. 2011;85:742-52 pubmed publisher
    b>Nef is an accessory protein critical for the ability of human and simian immunodeficiency viruses (HIV and SIV) to replicate efficiently in their respective hosts...
  57. Swingler S, Zhou J, Swingler C, Dauphin A, Greenough T, Jolicoeur P, et al. Evidence for a pathogenic determinant in HIV-1 Nef involved in B cell dysfunction in HIV/AIDS. Cell Host Microbe. 2008;4:63-76 pubmed publisher
    ..these hallmarks are caused by a soluble factor whose production by infected macrophages is induced by the HIV-1 Nef protein...
  58. Olivetta E, Mallozzi C, Ruggieri V, Pietraforte D, Federico M, Sanchez M. HIV-1 Nef induces p47(phox) phosphorylation leading to a rapid superoxide anion release from the U937 human monoblastic cell line. J Cell Biochem. 2009;106:812-22 pubmed publisher
    The Nef protein of the human immunodeficiency virus type 1 (HIV-1) plays a crucial role in AIDS pathogenesis by modifying host cell signaling pathways...
  59. Homann S, Tibroni N, Baumann I, Sertel S, Keppler O, Fackler O. Determinants in HIV-1 Nef for enhancement of virus replication and depletion of CD4+ T lymphocytes in human lymphoid tissue ex vivo. Retrovirology. 2009;6:6 pubmed publisher
    HIV-1 Nef critically contributes to AIDS in part by augmenting virus titers in infected individuals...
  60. Sauter D, Schindler M, Specht A, Landford W, M nch J, Kim K, et al. Tetherin-driven adaptation of Vpu and Nef function and the evolution of pandemic and nonpandemic HIV-1 strains. Cell Host Microbe. 2009;6:409-21 pubmed publisher
    ..SIVcpz, the immediate precursor of HIV-1, whose Vpu shares a common ancestry with SIVgsn/mus/mon Vpu, uses Nef rather than Vpu to counteract chimpanzee tetherin...
  61. Kumawat K, Pathak S, Spetz A, Kundu M, Basu J. Exogenous Nef is an inhibitor of Mycobacterium tuberculosis-induced tumor necrosis factor-alpha production and macrophage apoptosis. J Biol Chem. 2010;285:12629-37 pubmed publisher
    ..HIV Nef protein plays an important role in the pathogenesis of AIDS...
  62. Foster J, Denial S, Temple B, Garcia J. Mechanisms of HIV-1 Nef function and intracellular signaling. J Neuroimmune Pharmacol. 2011;6:230-46 pubmed publisher
    Advances in the last several years have enhanced mechanistic understanding of Nef-induced CD4 and MHCI downregulation and have suggested a new paradigm for analyzing Nef function...
  63. Stolp B, Fackler O. How HIV takes advantage of the cytoskeleton in entry and replication. Viruses. 2011;3:293-311 pubmed publisher
  64. El Far M, Isabelle C, Chomont N, Bourbonnière M, Fonseca S, Ancuta P, et al. Down-regulation of CTLA-4 by HIV-1 Nef protein. PLoS ONE. 2013;8:e54295 pubmed publisher
    HIV-1 Nef protein down-regulates several cell surface receptors through its interference with the cell sorting and trafficking machinery...
  65. Lee S, Park J, Jung J, Chung J. Nef induces apoptosis by activating JNK signaling pathway and inhibits NF-kappaB-dependent immune responses in Drosophila. J Cell Sci. 2005;118:1851-9 pubmed
    The human immunodeficiency virus type 1 (HIV-1) nef gene encodes a 27-kDa protein that plays a crucial role during AIDS pathogenesis, but its exact functional mechanism has not been fully elucidated and remains controversial...
  66. Ali A, Realegeno S, Yang O, Lewis M. Simultaneous assessment of CD4 and MHC-I downregulation by Nef primary isolates in the context of infection. J Virol Methods. 2009;161:297-304 pubmed publisher
    The HIV-1 Nef protein plays a key role in pathogenesis, as demonstrated by strong selective pressure to maintain its open reading frame, and disease attenuation when it is deleted...
  67. Arhel N, Lehmann M, Clauss K, Nienhaus G, Piguet V, Kirchhoff F. The inability to disrupt the immunological synapse between infected human T cells and APCs distinguishes HIV-1 from most other primate lentiviruses. J Clin Invest. 2009;119:2965-75 pubmed publisher
    ..HIV-1 and other primate lentiviruses use their Nef proteins to manipulate the T cell/APC contact zone, the immunological synapse (IS)...
  68. Pizzato M, Popova E, Gottlinger H. Nef can enhance the infectivity of receptor-pseudotyped human immunodeficiency virus type 1 particles. J Virol. 2008;82:10811-9 pubmed publisher
    b>Nef is an accessory protein of human immunodeficiency virus type 1 (HIV-1) that enhances the infectivity of progeny virions when expressed in virus-producing cells...
  69. Kyei G, Dinkins C, Davis A, Roberts E, Singh S, Dong C, et al. Autophagy pathway intersects with HIV-1 biosynthesis and regulates viral yields in macrophages. J Cell Biol. 2009;186:255-68 pubmed publisher
    ..This, however, does not occur, as the HIV protein Nef acts as an antiautophagic maturation factor through interactions with the autophagy regulatory factor Beclin 1, ..
  70. Gray L, Gabuzda D, Cowley D, Ellett A, Chiavaroli L, Wesselingh S, et al. CD4 and MHC class 1 down-modulation activities of nef alleles from brain- and lymphoid tissue-derived primary HIV-1 isolates. J Neurovirol. 2011;17:82-91 pubmed publisher
    Human immunodeficiency virus type 1 (HIV-1) nef undergoes adaptive evolution in the central nervous system (CNS), reflecting altered requirements for HIV-1 replication in macrophages/microglia and brain-specific immune selection ..
  71. Sugiyama R, Naganuma H, Nishitsuji H, Takaku H. Human immunodeficiency virus-1 Nef suppresses Hsp70-mediated Tat activation. FEBS Lett. 2011;585:3367-71 pubmed publisher
    ..Although previous reports have indicated that HIV-1 Nef positively or negatively regulates HIV-1 gene expression, the precise molecular mechanisms by which this occurs ..
  72. Khan K, Abbas W, Varin A, Kumar A, Di Martino V, Dichamp I, et al. HIV-1 Nef interacts with HCV Core, recruits TRAF2, TRAF5 and TRAF6, and stimulates HIV-1 replication in macrophages. J Innate Immun. 2013;5:639-56 pubmed publisher
    ..Here we show that TRAF2, TRAF5 and TRAF6 interact with the HIV-1 Nef protein, an immunomodulatory viral protein expressed and released by cells infected by the virus...
  73. Kasper M, Roeth J, Williams M, Filzen T, Fleis R, Collins K. HIV-1 Nef disrupts antigen presentation early in the secretory pathway. J Biol Chem. 2005;280:12840-8 pubmed
    Human immunodeficiency virus, type 1 Nef disrupts viral antigen presentation and promotes viral immune evasion from cytotoxic T lymphocytes...
  74. Specht A, DeGottardi M, Schindler M, Hahn B, Evans D, Kirchhoff F. Selective downmodulation of HLA-A and -B by Nef alleles from different groups of primate lentiviruses. Virology. 2008;373:229-37 pubmed
    It has been demonstrated that the HIV-1 NL4-3 and IIIB Nef alleles downregulate HLA-A and -B but not -C or -E from the cell surface...
  75. Hiyoshi M, Suzu S, Yoshidomi Y, Hassan R, Harada H, Sakashita N, et al. Interaction between Hck and HIV-1 Nef negatively regulates cell surface expression of M-CSF receptor. Blood. 2008;111:243-50 pubmed
    b>Nef is a multifunctional pathogenetic protein of HIV-1, the interaction of which with Hck, a Src tyrosine kinase highly expressed in macrophages, has been shown to be responsible for the development of AIDS...
  76. Mitchell R, Chaudhuri R, Lindwasser O, Tanaka K, Lau D, Murillo R, et al. Competition model for upregulation of the major histocompatibility complex class II-associated invariant chain by human immunodeficiency virus type 1 Nef. J Virol. 2008;82:7758-67 pubmed publisher
    The human immunodeficiency virus type 1 (HIV-1) Nef protein upregulates the expression of the invariant chain (Ii)/major histocompatibility complex class II (MHC-II) complex at the cell surface...
  77. Olivieri K, Agopian K, Mukerji J, Gabuzda D. Evidence for adaptive evolution at the divergence between lymphoid and brain HIV-1 nef genes. AIDS Res Hum Retroviruses. 2010;26:495-500 pubmed publisher
    ..The role of HIV Nef and other accessory proteins in HAND pathogenesis is unclear...
  78. Fan Y, Liu C, Qin X, Wang Y, Han Y, Zhou Y. The role of ERK1/2 signaling pathway in Nef protein upregulation of the expression of the intercellular adhesion molecule 1 in endothelial cells. Angiology. 2010;61:669-78 pubmed publisher
    ..HIV-1 accessory protein negative regulate factor (Nef) has been shown to be very important for high virus replication and disease progression...
  79. 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
    The Nef protein is an essential factor for lentiviral pathogenesis in humans and other simians. Despite a multitude of functions attributed to this protein, the exact role of Nef in disease progression remains unclear...
  80. Mangino G, Percario Z, Fiorucci G, Vaccari G, Manrique S, Romeo G, et al. In vitro treatment of human monocytes/macrophages with myristoylated recombinant Nef of human immunodeficiency virus type 1 leads to the activation of mitogen-activated protein kinases, IkappaB kinases, and interferon regulatory factor 3 and to the r. J Virol. 2007;81:2777-91 pubmed
    The viral protein Nef is a virulence factor that plays multiple roles during the early and late phases of human immunodeficiency virus (HIV) replication...
  81. Quaranta M, Napolitano A, Sanchez M, Giordani L, Mattioli B, Viora M. HIV-1 Nef impairs the dynamic of DC/NK crosstalk: different outcome of CD56(dim) and CD56(bright) NK cell subsets. FASEB J. 2007;21:2323-34 pubmed
    ..The accessory HIV-1 Nef protein is a crucial determinant for viral replication and pathogenesis...
  82. Narute P, Smithgall T. Nef alleles from all major HIV-1 clades activate Src-family kinases and enhance HIV-1 replication in an inhibitor-sensitive manner. PLoS ONE. 2012;7:e32561 pubmed publisher
    The HIV-1 accessory factor Nef is essential for high-titer viral replication and AIDS progression. Nef function requires interaction with many host cell proteins, including specific members of the Src kinase family...
  83. Lamers S, Fogel G, Singer E, Salemi M, Nolan D, Huysentruyt L, et al. HIV-1 Nef in macrophage-mediated disease pathogenesis. Int Rev Immunol. 2012;31:432-50 pubmed publisher
    ..Within macrophages, the HIV-1 regulatory protein "Nef" can modulate surface receptors, interact with signaling pathways, and promote specific environments that ..
  84. Mujawar Z, Tamehiro N, Grant A, Sviridov D, Bukrinsky M, Fitzgerald M. Mutation of the ATP cassette binding transporter A1 (ABCA1) C-terminus disrupts HIV-1 Nef binding but does not block the Nef enhancement of ABCA1 protein degradation. Biochemistry. 2010;49:8338-49 pubmed publisher
    ..The HIV-1 Nef protein can impair ATP cassette binding transporter A1 (ABCA1) cholesterol efflux from macrophages, a potentially ..
  85. Corró G, Rocco C, De Candia C, Catano G, Turk G, Mangano A, et al. Genetic and functional analysis of HIV type 1 nef gene derived from long-term nonprogressor children: association of attenuated variants with slow progression to pediatric AIDS. AIDS Res Hum Retroviruses. 2012;28:1617-26 pubmed publisher
    ..to AIDS is multifactorial being affected by host and viral factors, including the HIV-encoded negative factor (Nef)...
  86. Rajapaksa U, Li D, Peng Y, McMichael A, Dong T, Xu X. HLA-B may be more protective against HIV-1 than HLA-A because it resists negative regulatory factor (Nef) mediated down-regulation. Proc Natl Acad Sci U S A. 2012;109:13353-8 pubmed publisher
    ..HIV-1 negative regulatory factor (Nef) mediates down-regulation of surface expression of class I HLA (HLA-I) and may therefore impair immune recognition ..
  87. Husain M, D Agati V, He J, Klotman M, Klotman P. HIV-1 Nef induces dedifferentiation of podocytes in vivo: a characteristic feature of HIVAN. AIDS. 2005;19:1975-80 pubmed
    To determine the specific role of Nef in the pathogenesis of HIV-associated nephropathy...
  88. Jin Y, Cai C, Zhang X, Burakoff S. Lysine 144, a ubiquitin attachment site in HIV-1 Nef, is required for Nef-mediated CD4 down-regulation. J Immunol. 2008;180:7878-86 pubmed
    b>Nef is a HIV-1 accessory protein critical for the replication of the virus and the development of AIDS. The major pathological activity of Nef is the down-regulation of CD4, the primary receptor of HIV-1 infection...
  89. Yang F, Liu C, Qin X, Shi J. [HIV-1 Nef regulates ICAM-1 expression on endothelial cells via Erk /Mapk signaling pathway]. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2010;26:44-6 pubmed
    To explore the effect of HIV-1 Nef on the ICAM-1 expression of endothelial cells ECV-304 and its signaling pathways. ICAM-1 expression on the endothelial cells ECV-304 was detected by Western blot and FCM assay...
  90. Park I, He J. HIV-1 Nef-mediated inhibition of T cell migration and its molecular determinants. J Leukoc Biol. 2009;86:1171-8 pubmed publisher
    ..Previous studies have shown that HIV-1 Nef inhibits T cell chemotaxis in response to the physiological ligand SDF-1alpha [( 1) ]...
  91. Mwimanzi P, Hasan Z, Hassan R, Suzu S, Takiguchi M, Ueno T. Effects of naturally-arising HIV Nef mutations on cytotoxic T lymphocyte recognition and Nef's functionality in primary macrophages. Retrovirology. 2011;8:50 pubmed publisher
    ..Here, we tested two naturally-arising mutations located in the well-conserved polyproline region of Nef for their effects on CTL recognition, Nef's functionality, and viral replication capacity in macrophages...
  92. Heigele A, Schindler M, Gnanadurai C, Leonard J, Collins K, Kirchhoff F. Down-modulation of CD8?? is a fundamental activity of primate lentiviral Nef proteins. J Virol. 2012;86:36-48 pubmed publisher
    It is well established that the Nef proteins of human and simian immunodeficiency viruses (HIV and SIV) modulate major histocompatibility complex class I (MHC-I) cell surface expression to protect infected cells against lysis by ..
  93. Ren X, Park S, Bonifacino J, Hurley J. How HIV-1 Nef hijacks the AP-2 clathrin adaptor to downregulate CD4. elife. 2014;3:e01754 pubmed publisher
    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...
  94. Dennis C, Baron A, Grossmann J, Mazaleyrat S, Harris M, Jaeger J. Co-translational myristoylation alters the quaternary structure of HIV-1 Nef in solution. Proteins. 2005;60:658-69 pubmed
    We have studied the solution properties of Nef, a 24-kDa cotranslationally myristoylated protein produced by HIV-1 and other primate lentiviruses...
  95. Dai L, Stevenson M. A novel motif in HIV-1 Nef that regulates MIP-1beta chemokine release in macrophages. J Virol. 2010;84:8327-31 pubmed publisher
    All primate lentiviruses encode Nef, an accessory protein that is important for viral pathogenicity in vivo...
  96. Stolp B, Imle A, Coelho F, Hons M, Gorina R, Lyck R, et al. HIV-1 Nef interferes with T-lymphocyte circulation through confined environments in vivo. Proc Natl Acad Sci U S A. 2012;109:18541-6 pubmed publisher
    HIV-1 negative factor (Nef) elevates virus replication and contributes to immune evasion in vivo. As one of its established in vitro activities, Nef interferes with T-lymphocyte chemotaxis by reducing host cell actin dynamics...
  97. Sowrirajan B, Barker E. The natural killer cell cytotoxic function is modulated by HIV-1 accessory proteins. Viruses. 2011;3:1091-111 pubmed publisher
    ..In addition, the accessory protein Nef removes the inhibitory ligands HLA-A and -B...