HIV-1 Nef: A multifaceted modulator of T cell receptor signaling

Cell Communication and Signaling

Volumn 10, Issue , 2012, Pages

  Abraham, Libin ^a,b   Fackler, Oliver T ^a  

^a UNIVERSITY HOSPITAL HEIDELBERG   (Germany)

^b Hartmut Hoffmann Berling International Graduate School of Molecular and Cellular Biology   (Germany)

Author keywords

HIV AIDS; Microclusters; Nef; T cell receptor signaling

Indexed keywords

CELL SURFACE RECEPTOR; MITOGEN ACTIVATED PROTEIN KINASE; NEF PROTEIN; RAS PROTEIN; T LYMPHOCYTE RECEPTOR;

CELL ACTIVITY; CELL CULTURE; CELL VACUOLE; CYTOSKELETON; ENZYME ACTIVATION; HOST; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS 1 INFECTION; INTRACELLULAR TRANSPORT; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN INTERACTION; REVIEW; SIGNAL TRANSDUCTION; T LYMPHOCYTE; TRANS GOLGI NETWORK; VIRUS PATHOGENESIS; VIRUS REPLICATION;

HUMAN IMMUNODEFICIENCY VIRUS 1;

EID: 84871795476     PISSN: None     EISSN: 1478811X     Source Type: Journal    
DOI: 10.1186/1478-811X-10-39     Document Type: Review

References (126)

1. T cell activation. Smith-Garvin JE, Koretzky GA, Jordan MS, Annu Rev Immunol 2009 27 591 619 10.1146/annurev.immunol.021908.132706 19132916
2. Three-dimensional segregation of supramolecular activation clusters in T cells. Monks CR, Freiberg BA, Kupfer H, Sciaky N, Kupfer A, Nature 1998 395 82 86 10.1038/25764 9738502
3. The immunological synapse: a molecular machine controlling T cell activation. Grakoui A, Bromley SK, Sumen C, Davis MM, Shaw AS, Allen PM, Dustin ML, Science 1999 285 221 227 10.1126/science.285.5425.221 10398592
4. The immunological synapse: a dynamic platform for local signaling. Krummel MF, Cahalan MD, J Clin Immunol 2010 30 364 372 10.1007/s10875-010-9393-6 20390326
5. Understanding the structure and function of the immunological synapse. Dustin ML, Chakraborty AK, Shaw AS, Cold Spring Harb Perspect Biol 2010 2 002311 10.1101/cshperspect.a002311 20843980
6. Cell signaling by receptor tyrosine kinases. Schlessinger J, Cell 2000 103 211 225 10.1016/S0092-8674(00)00114-8 11057895
7. Signal transduction mediated by the T cell antigen receptor: the role of adapter proteins. Samelson LE, Annu Rev Immunol 2002 20 371 394 10.1146/annurev.immunol.20.092601.111357 11861607
8. New insights into the molecular mechanisms of store-operated Ca2+ signaling in T cells. Luik RM, Lewis RS, Trends Mol Med 2007 13 103 107 10.1016/j.molmed.2007.01.004 17267286
9. Spatial and temporal dynamics of T cell receptor signaling with a photoactivatable agonist. Huse M, Klein LO, Girvin AT, Faraj JM, Li QJ, Kuhns MS, Davis MM, Immunity 2007 27 76 88 10.1016/j.immuni.2007.05.017 17629516
10. T cell activation and the cytoskeleton. Acuto O, Cantrell D, Annu Rev Immunol 2000 18 165 184 10.1146/annurev.immunol.18.1.165 10837056
11. Regulation of T-cell activation by the cytoskeleton. Billadeau DD, Nolz JC, Gomez TS, Nat Rev Immunol 2007 7 131 143 10.1038/nri2021 17259969
12. Lck regulates the tyrosine phosphorylation of the T cell receptor subunits and ZAP-70 in murine thymocytes. van Oers NS, Killeen N, Weiss A, J Exp Med 1996 183 1053 1062 10.1084/jem.183.3.1053 8642247
13. Tailoring T-cell receptor signals by proximal negative feedback mechanisms. Acuto O, Di Bartolo V, Michel F, Nat Rev Immunol 2008 8 699 712 10.1038/nri2397 18728635
14. The 21- and 23-kD forms of TCR zeta are generated by specific ITAM phosphorylations. van Oers NS, Tohlen B, Malissen B, Moomaw CR, Afendis S, Slaughter CA, Nat Immunol 2000 1 322 328 10.1038/79774 11017104
15. Phosphorylation of SLP-76 by the ZAP-70 protein-tyrosine kinase is required for T-cell receptor function. Bubeck Wardenburg J, Fu C, Jackman JK, Flotow H, Wilkinson SE, Williams DH, Johnson R, Kong G, Chan AC, Findell PR, J Biol Chem 1996 271 19641 19644 10.1074/jbc.271.33.19641 8702662
16. LAT: the ZAP-70 tyrosine kinase substrate that links T cell receptor to cellular activation. Zhang W, Sloan-Lancaster J, Kitchen J, Trible RP, Samelson LE, Cell 1998 92 83 92 10.1016/S0092-8674(00)80901-0 9489702
17. The LAT story: a tale of cooperativity, coordination, and choreography. Balagopalan L, Coussens NP, Sherman E, Samelson LE, Sommers CL, Cold Spring Harb Perspect Biol 2010 2 005512 10.1101/cshperspect.a005512 20610546
18. SLP76 and SLP65: complex regulation of signalling in lymphocytes and beyond. Koretzky GA, Abtahian F, Silverman MA, Nat Rev Immunol 2006 6 67 78 10.1038/nri1750 16493428
19. High resolution mapping of mast cell membranes reveals primary and secondary domains of Fc(epsilon)RI and LAT. Wilson BS, Pfeiffer JR, Surviladze Z, Gaudet EA, Oliver JM, J Cell Biol 2001 154 645 658 10.1083/jcb.200104049 11489921
20. Plasma membrane-associated proteins are clustered into islands attached to the cytoskeleton. Lillemeier BF, Pfeiffer JR, Surviladze Z, Wilson BS, Davis MM, Proc Natl Acad Sci USA 2006 103 18992 18997 10.1073/pnas.0609009103 17146050
21. Endothelial nitric oxide synthase regulates N-Ras activation on the Golgi complex of antigen-stimulated T cells. Ibiza S, Perez-Rodriguez A, Ortega A, Martinez-Ruiz A, Barreiro O, Garcia-Dominguez CA, Victor VM, Esplugues JV, Rojas JM, Sanchez-Madrid F, Serrador JM, Proc Natl Acad Sci USA 2008 105 10507 10512 10.1073/pnas.0711062105 18641128
22. The lymphocyte function-associated antigen-1 receptor costimulates plasma membrane Ras via phospholipase D2. Mor A, Campi G, Du G, Zheng Y, Foster DA, Dustin ML, Philips MR, Nat Cell Biol 2007 9 713 719 10.1038/ncb1592 17486117
23. Ras activation in Jurkat T cells following low-grade stimulation of the T-cell receptor is specific to N-Ras and occurs only on the Golgi apparatus. Perez De Castro I, Bivona TG, Philips MR, Pellicer A, Mol Cell Biol 2004 24 3485 3496 10.1128/MCB.24.8.3485-3496.2004 15060167
24. Endomembrane trafficking of ras: the CAAX motif targets proteins to the ER and Golgi. Choy E, Chiu VK, Silletti J, Feoktistov M, Morimoto T, Michaelson D, Ivanov IE, Philips MR, Cell 1999 98 69 80 10.1016/S0092-8674(00)80607-8 10412982
25. H-ras but not K-ras traffics to the plasma membrane through the exocytic pathway. Apolloni A, Prior IA, Lindsay M, Parton RG, Hancock JF, Mol Cell Biol 2000 20 2475 2487 10.1128/MCB.20.7.2475-2487.2000 10713171
26. Visualizing Ras signalling in real-time. Walker SA, Lockyer PJ, J Cell Sci 2004 117 2879 2886 10.1242/jcs.01285 15197243
27. Compartmentalized Ras/MAPK signaling. Mor A, Philips MR, Annu Rev Immunol 2006 24 771 800 10.1146/annurev.immunol.24.021605.090723 16551266
28. Ras/MAPK signaling from endomembranes. Fehrenbacher N, Bar-Sagi D, Philips M, Mol Oncol 2009 3 297 307 10.1016/j.molonc.2009.06.004 19615955
29. T cell receptor-proximal signals are sustained in peripheral microclusters and terminated in the central supramolecular activation cluster. Varma R, Campi G, Yokosuka T, Saito T, Dustin ML, Immunity 2006 25 117 127 10.1016/j.immuni.2006.04.010 16860761
30. New insights into the T cell synapse from single molecule techniques. Dustin ML, Depoil D, Nat Rev Immunol 2011 11 672 684 10.1038/nri3066 21904389
31. T cell receptor ligation induces the formation of dynamically regulated signaling assemblies. Bunnell SC, Hong DI, Kardon JR, Yamazaki T, McGlade CJ, Barr VA, Samelson LE, J Cell Biol 2002 158 1263 1275 10.1083/jcb.200203043 12356870
32. The immunological synapse, TCR microclusters, and T cell activation. Yokosuka T, Saito T, Curr Top Microbiol Immunol 2010 340 81 107 10.1007/978-3-642-03858-7-5 19960310
33. Actin and agonist MHC-peptide complex-dependent T cell receptor microclusters as scaffolds for signaling. Campi G, Varma R, Dustin ML, J Exp Med 2005 202 1031 1036 10.1084/jem.20051182 16216891
34. Newly generated T cell receptor microclusters initiate and sustain T cell activation by recruitment of Zap70 and SLP-76. Yokosuka T, Sakata-Sogawa K, Kobayashi W, Hiroshima M, Hashimoto-Tane A, Tokunaga M, Dustin ML, Saito T, Nat Immunol 2005 6 1253 1262 10.1038/ni1272 16273097
35. Dynamic regulation of T-cell costimulation through TCR-CD28 microclusters. Yokosuka T, Saito T, Immunol Rev 2009 229 27 40 10.1111/j.1600-065X.2009.00779.x 19426213
36. Persistence of cooperatively stabilized signaling clusters drives T-cell activation. Bunnell SC, Singer AL, Hong DI, Jacque BH, Jordan MS, Seminario MC, Barr VA, Koretzky GA, Samelson LE, Mol Cell Biol 2006 26 7155 7166 10.1128/MCB.00507-06 16980618
37. Multiple microclusters: diverse compartments within the immune synapse. Bunnell SC, Curr Top Microbiol Immunol 2010 340 123 154 10.1007/978-3-642-03858- 7-7 19960312
38. Microtubule-organizing center polarity and the immunological synapse: protein kinase C and beyond. Huse M, Front Immunol 2012 3 235 23060874
39. End-binding protein 1 controls signal propagation from the T cell receptor. Martin-Cofreces NB, Baixauli F, Lopez MJ, Gil D, Monjas A, Alarcon B, Sanchez-Madrid F, EMBO J 2012 31 4140 4152 10.1038/emboj.2012.242 22922463
40. Microtubule dynamics and signal transduction at the immunological synapse: new partners and new connections. Lasserre R, Alcover A, EMBO J 2012 31 4100 4102 10.1038/emboj.2012.276 23047155
41. Quiescent T lymphocytes as an inducible virus reservoir in HIV-1 infection. Bukrinsky MI, Stanwick TL, Dempsey MP, Stevenson M, Science 1991 254 423 427 10.1126/science.1925601 1925601
42. Cellular tropism of the human retrovirus HTLV-III/LAV. I. Role of T cell activation and expression of the T4 antigen. McDougal JS, Mawle A, Cort SP, Nicholson JK, Cross GD, Scheppler-Campbell JA, Hicks D, Sligh J, J Immunol 1985 135 3151 3162 2995487
43. HIV-1 pathogenesis. Stevenson M, Nat Med 2003 9 853 860 10.1038/nm0703-853 12835705
44. Modulation of the immunological synapse: a key to HIV-1 pathogenesis? Fackler OT, Alcover A, Schwartz O, Nat Rev Immunol 2007 7 310 317 10.1038/nri2041 17380160
45. HIV-1 entry into quiescent primary lymphocytes: molecular analysis reveals a labile, latent viral structure. Zack JA, Arrigo SJ, Weitsman SR, Go AS, Haislip A, Chen IS, Cell 1990 61 213 222 10.1016/0092-8674(90)90802-L 2331748
46. HIV-1 replication is controlled at the level of T cell activation and proviral integration. Stevenson M, Stanwick TL, Dempsey MP, Lamonica CA, EMBO J 1990 9 1551 1560 2184033
47. Recovery of replication-competent HIV despite prolonged suppression of plasma viremia. Wong JK, Hezareh M, Gunthard HF, Havlir DV, Ignacio CC, Spina CA, Richman DD, Science 1997 278 1291 1295 10.1126/science.278.5341.1291 9360926
48. Incompletely reverse-transcribed human immunodeficiency virus type 1 genomes in quiescent cells can function as intermediates in the retroviral life cycle. Zack JA, Haislip AM, Krogstad P, Chen IS, J Virol 1992 66 1717 1725 1371173
49. Cellular APOBEC3G restricts HIV-1 infection in resting CD4+ T cells. Chiu YL, Soros VB, Kreisberg JF, Stopak K, Yonemoto W, Greene WC, Nature 2005 435 108 114 10.1038/nature03493 15829920
50. Selective transcription and modulation of resting T cell activity by preintegrated HIV DNA. Wu Y, Marsh JW, Science 2001 293 1503 1506 10.1126/science.1061548 11520990
51. SAMHD1 is the dendritic- and myeloid-cell-specific HIV-1 restriction factor counteracted by Vpx. Laguette N, Sobhian B, Casartelli N, Ringeard M, Chable-Bessia C, Segeral E, Yatim A, Emiliani S, Schwartz O, Benkirane M, Nature 2011 474 654 657 10.1038/nature10117 21613998
52. Vpx relieves inhibition of HIV-1 infection of macrophages mediated by the SAMHD1 protein. Hrecka K, Hao C, Gierszewska M, Swanson SK, Kesik-Brodacka M, Srivastava S, Florens L, Washburn MP, Skowronski J, Nature 2011 474 658 661 10.1038/nature10195 21720370
53. SAMHD1 restricts HIV-1 infection in resting CD4(+) T cells. Baldauf HM, Pan X, Erikson E, Schmidt S, Daddacha W, Burggraf M, Schenkova K, Ambiel I, Wabnitz G, Gramberg T, et al. Nat Med 2012 18 1682 1689 10.1038/nm.2964 22972397
54. Nuclear retention of multiply spliced HIV-1 RNA in resting CD4+ T cells. Lassen KG, Ramyar KX, Bailey JR, Zhou Y, Siliciano RF, PLoS Pathog 2006 2 68 10.1371/journal.ppat.0020068 16839202
55. Endogenous factors enhance HIV infection of tissue naive CD4 T cells by stimulating high molecular mass APOBEC3G complex formation. Kreisberg JF, Yonemoto W, Greene WC, J Exp Med 2006 203 865 870 10.1084/jem.20051856 16606671
56. Host control of HIV-1 parasitism in T cells by the nuclear factor of activated T cells. Kinoshita S, Chen BK, Kaneshima H, Nolan GP, Cell 1998 95 595 604 10.1016/S0092-8674(00)81630-X 9845362
57. The gene product Murr1 restricts HIV-1 replication in resting CD4+ lymphocytes. Ganesh L, Burstein E, Guha-Niyogi A, Louder MK, Mascola JR, Klomp LW, Wijmenga C, Duckett CS, Nabel GJ, Nature 2003 426 853 857 10.1038/nature02171 14685242
58. HIV-1 actively replicates in naive CD4(+) T cells residing within human lymphoid tissues. Eckstein DA, Penn ML, Korin YD, Scripture-Adams DD, Zack JA, Kreisberg JF, Roederer M, Sherman MP, Chin PS, Goldsmith MA, Immunity 2001 15 671 682 10.1016/S1074-7613(01)00217-5 11672548
59. How T lymphocytes switch between life and death. Arnold R, Brenner D, Becker M, Frey CR, Krammer PH, Eur J Immunol 2006 36 1654 1658 10.1002/eji.200636197 16791883
60. T cell homeostasis in steady state and lymphopenic conditions. Bourgeois C, Stockinger B, Immunol Lett 2006 107 89 92 10.1016/j.imlet.2006.08.001 16963128
61. Brief report: absence of intact nef sequences in a long-term survivor with nonprogressive HIV-1 infection. Kirchhoff F, Greenough TC, Brettler DB, Sullivan JL, Desrosiers RC, N Engl J Med 1995 332 228 232 10.1056/ NEJM199501263320405 7808489
62. Genomic structure of an attenuated quasi species of HIV-1 from a blood transfusion donor and recipients. Deacon NJ, Tsykin A, Solomon A, Smith K, Ludford-Menting M, Hooker DJ, McPhee DA, Greenway AL, Ellett A, Chatfield C, et al. Science 1995 270 988 991 10.1126/science.270.5238.988 7481804
63. Importance of the nef gene for maintenance of high virus loads and for development of AIDS. Kestler HW 3rd, Ringler DJ, Mori K, Panicali DL, Sehgal PK, Daniel MD, Desrosiers RC, Cell 1991 65 651 662 10.1016/0092-8674(91)90097-I 2032289
64. Human immunodeficiency virus (HIV) type-1, HIV-2 and simian immunodeficiency virus Nef proteins. Laguette N, Bregnard C, Benichou S, Basmaciogullari S, Mol Aspects Med 2010 31 418 433 10.1016/j.mam.2010.05.003 20594957
65. Structure-function relationships in HIV-1 Nef. Geyer M, Fackler OT, Peterlin BM, EMBO Rep 2001 2 580 585 10.1093/embo-reports/kve141 11463741
66. Human immunodeficiency virus type 1 Nef: adapting to intracellular trafficking pathways. Roeth JF, Collins KL, Microbiol Mol Biol Rev 2006 70 548 563 10.1128/MMBR.00042-05 16760313
67. How HIV takes advantage of the cytoskeleton in entry and replication. Stolp B, Fackler OT, Viruses 2011 3 293 311 10.3390/v3040293 21994733
68. Identification of a nef allele that causes lymphocyte activation and acute disease in macaque monkeys. Du Z, Lang SM, Sasseville VG, Lackner AA, Ilyinskii PO, Daniel MD, Jung JU, Desrosiers RC, Cell 1995 82 665 674 10.1016/0092-8674(95)90038-1 7664345
69. Activation of the T-cell receptor signaling pathway by Nef from an aggressive strain of simian immunodeficiency virus. Luo W, Peterlin BM, J Virol 1997 71 9531 9537 9371616
70. Mutation of a diacidic motif in SIV-PBj Nef impairs T-cell activation and enteropathic disease. Tschulena U, Sanzenbacher R, Muhlebach MD, Berger A, Munch J, Schindler M, Kirchhoff F, Plesker R, Coulibaly C, Panitz S, et al. Retrovirology 2011 8 14 10.1186/1742-4690-8-14 21366921
71. HIV-1 Nef leads to inhibition or activation of T cells depending on its intracellular localization. Baur AS, Sawai ET, Dazin P, Fantl WJ, Cheng-Mayer C, Peterlin BM, Immunity 1994 1 373 384 10.1016/1074-7613(94)90068-X 7882168
72. The role of HIV1 Nef in T-cell activation: Nef impairs induction of Th1 cytokines and interacts with the Src family tyrosine kinase Lck. Collette Y, Dutartre H, Benziane A, Olive D, Res Virol 1997 148 52 58 10.1016/S0923-2516(97) 81914-0 9017835
73. Expression of the type 1 human immunodeficiency virus Nef protein in T cells prevents antigen receptor-mediated induction of interleukin 2 mRNA. Luria S, Chambers I, Berg P, Proc Natl Acad Sci USA 1991 88 5326 5330 10.1073/pnas.88.12.5326 2052609
74. Human immunodeficiency virus type 1 Nef protein inhibits NF-kappa B induction in human T cells. Niederman TM, Garcia JV, Hastings WR, Luria S, Ratner L, J Virol 1992 66 6213 6219 1527859
75. Vav exchange factor counteracts the HIV-1 Nef-mediated decrease of plasma membrane GM1 and NF-AT activity in T cells. Tuosto L, Marinari B, Andreotti M, Federico M, Piccolella E, Eur J Immunol 2003 33 2186 2196 10.1002/eji.200323682 12884293
76. Nef is physically recruited into the immunological synapse and potentiates T cell activation early after TCR engagement. Fenard D, Yonemoto W, de Noronha C, Cavrois M, Williams SA, Greene WC, J Immunol 2005 175 6050 6057 16237100
77. Hyper-responsiveness to stimulation of human immunodeficiency virus-infected CD4+ T cells requires Nef and Tat virus gene products and results from higher NFAT, NF-kappaB, and AP-1 induction. Fortin JF, Barat C, Beausejour Y, Barbeau B, Tremblay MJ, J Biol Chem 2004 279 39520 39531 10.1074/jbc.M407477200 15258149
78. Human immunodeficiency virus type 1 Nef binds directly to Lck and mitogen-activated protein kinase, inhibiting kinase activity. Greenway A, Azad A, Mills J, McPhee D, J Virol 1996 70 6701 6708 8794306
79. Induction of fas ligand expression by an acutely lethal simian immunodeficiency virus, SIVsmmPBj14. Hodge S, Novembre FJ, Whetter L, Gelbard HA, Dewhurst S, Virology 1998 252 354 363 10.1006/viro.1998.9477 9878614
80. Modulation of specific surface receptors and activation sensitization in primary resting CD4+ T lymphocytes by the Nef protein of HIV-1. Keppler OT, Tibroni N, Venzke S, Rauch S, Fackler OT, J Leukoc Biol 2006 79 616 627 16365153
81. HIV-1 Nef interacts with inositol trisphosphate receptor to activate calcium signaling in T cells. Manninen A, Saksela K, J Exp Med 2002 195 1023 1032 10.1084/jem.20012039 11956293
82. Synergistic activation of NFAT by HIV-1 nef and the Ras/MAPK pathway. Manninen A, Renkema GH, Saksela K, J Biol Chem 2000 275 16513 16517 10.1074/jbc.M910032199 10748182
83. Nef-mediated suppression of T cell activation was lost in a lentiviral lineage that gave rise to HIV-1. Schindler M, Munch J, Kutsch O, Li H, Santiago ML, Bibollet-Ruche F, Muller-Trutwin MC, Novembre FJ, Peeters M, Courgnaud V, et al. Cell 2006 125 1055 1067 10.1016/j.cell.2006.04.033 16777597
84. HIV Nef increases T cell ERK MAP kinase activity. Schrager JA, Der Minassian V, Marsh JW, J Biol Chem 2002 277 6137 6142 10.1074/jbc.M107322200 11726657
85. HIV-1 Nef increases T cell activation in a stimulus-dependent manner. Schrager JA, Marsh JW, Proc Natl Acad Sci USA 1999 96 8167 8172 10.1073/pnas.96.14.8167 10393966
86. Nef triggers a transcriptional program in T cells imitating single-signal T cell activation and inducing HIV virulence mediators. Simmons A, Aluvihare V, McMichael A, Immunity 2001 14 763 777 10.1016/S1074-7613(01)00158-3 11420046
87. The Nef protein of HIV-1 associates with rafts and primes T cells for activation. Wang JK, Kiyokawa E, Verdin E, Trono D, Proc Natl Acad Sci USA 2000 97 394 399 10.1073/pnas.97.1.394 10618429
88. The HIV-1 Nef protein has a dual role in T cell receptor signaling in infected CD4+ T lymphocytes. Neri F, Giolo G, Potesta M, Petrini S, Doria M, Virology 2011 410 316 326 10.1016/j.virol.2010.11.018 21176845
89. The HIV-1 pathogenicity factor Nef interferes with maturation of stimulatory T-lymphocyte contacts by modulation of N-Wasp activity. Haller C, Rauch S, Michel N, Hannemann S, Lehmann MJ, Keppler OT, Fackler OT, J Biol Chem 2006 281 19618 19630 10.1074/jbc.M513802200 16687395
90. Inhibition of T-cell receptor-induced actin remodeling and relocalization of Lck are evolutionarily conserved activities of lentiviral Nef proteins. Rudolph JM, Eickel N, Haller C, Schindler M, Fackler OT, J Virol 2009 83 11528 11539 10.1128/JVI.01423-09 19726522
91. Lentiviral Nef proteins utilize PAK2-mediated deregulation of cofilin as a general strategy to interfere with actin remodeling. Stolp B, Abraham L, Rudolph JM, Fackler OT, J Virol 2010 84 3935 3948 10.1128/JVI.02467-09 20147394
92. The inability to disrupt the immunological synapse between infected human T cells and APCs distinguishes HIV-1 from most other primate lentiviruses. Arhel N, Lehmann M, Clauss K, Nienhaus GU, Piguet V, Kirchhoff F, J Clin Invest 2009 119 2965 2975 19759518
93. Separable functions of Nef disrupt two aspects of T cell receptor machinery: CD4 expression and CD3 signaling. Iafrate AJ, Bronson S, Skowronski J, EMBO J 1997 16 673 684 10.1093/emboj/16.4.673 9049297
94. Association of simian immunodeficiency virus Nef with the T-cell receptor (TCR) zeta chain leads to TCR down-modulation. Bell I, Ashman C, Maughan J, Hooker E, Cook F, Reinhart TA, J Gen Virol 1998 79 Pt 11 2717 2727 9820147
95. Cooperative interactions of simian immunodeficiency virus Nef, AP-2, and CD3-zeta mediate the selective induction of T-cell receptor-CD3 endocytosis. Swigut T, Greenberg M, Skowronski J, J Virol 2003 77 8116 8126 10.1128/JVI.77.14.8116-8126.2003 12829850
96. Implications of Nef: host cell interactions in viral persistence and progression to AIDS. Arhel NJ, Kirchhoff F, Curr Top Microbiol Immunol 2009 339 147 175 10.1007/978-3-642-02175-6-8 20012528
97. Mechanisms of HIV-1 Nef function and intracellular signaling. Foster JL, Denial SJ, Temple BR, Garcia JV, J Neuroimmune Pharmacol 2011 6 230 246 10.1007/s11481-011-9262-y 21336563
98. Human immunodeficiency virus type-1 infection impairs the formation of the immunological synapse. Thoulouze MI, Sol-Foulon N, Blanchet F, Dautry-Varsat A, Schwartz O, Alcover A, Immunity 2006 24 547 561 10.1016/j.immuni.2006.02.016 16713973
99. HIV-1 Nef employs two distinct mechanisms to modulate Lck subcellular localization and TCR induced actin remodeling. Haller C, Rauch S, Fackler OT, PLoS One 2007 2 1212 10.1371/journal.pone.0001212 18030346
100. HIV-1 Nef compensates for disorganization of the immunological synapse by inducing trans-Golgi network-associated Lck signaling. Pan X, Rudolph JM, Abraham L, Habermann A, Haller C, Krijnse-Locker J, Fackler OT, Blood 2012 119 786 797 10.1182/blood-2011-08-373209 22123847
101. The N-terminus of Nef from HIV-1/SIV associates with a protein complex containing Lck and a serine kinase. Baur AS, Sass G, Laffert B, Willbold D, Cheng-Mayer C, Peterlin BM, Immunity 1997 6 283 291 10.1016/S1074-7613(00)80331- 3 9075929
102. Novel (n)PKC kinases phosphorylate Nef for increased HIV transcription, replication and perinuclear targeting. Wolf D, Giese SI, Witte V, Krautkramer E, Trapp S, Sass G, Haller C, Blume K, Fackler OT, Baur AS, Virology 2008 370 45 54 10.1016/j.virol.2007.08.015 17904606
103. Induction of HIV transcription by Nef involves Lck activation and protein kinase C theta raft recruitment leading to activation of ERK1/2 but not NF kappa B. Witte V, Laffert B, Gintschel P, Krautkramer E, Blume K, Fackler OT, Baur AS, J Immunol 2008 181 8425 8432 19050260
104. Sequential interactions of the TCR with two distinct cytoplasmic tyrosine kinases. Iwashima M, Irving BA, van Oers NS, Chan AC, Weiss A, Science 1994 263 1136 1139 10.1126/science.7509083 7509083
105. Lck regulates the threshold of activation in primary T cells, while both Lck and Fyn contribute to the magnitude of the extracellular signal-related kinase response. Lovatt M, Filby A, Parravicini V, Werlen G, Palmer E, Zamoyska R, Mol Cell Biol 2006 26 8655 8665 10.1128/MCB.00168-06 16966372
106. T-cell receptor proximal signaling via the Src-family kinases, Lck and Fyn, influences T-cell activation, differentiation, and tolerance. Salmond RJ, Filby A, Qureshi I, Caserta S, Zamoyska R, Immunol Rev 2009 228 9 22 10.1111/j.1600-065X.2008.00745.x 19290918
107. Function of the Src-family kinases, Lck and Fyn, in T-cell development and activation. Palacios EH, Weiss A, Oncogene 2004 23 7990 8000 10.1038/sj.onc.1208074 15489916
108. The influence of the src-family kinases, Lck and Fyn, on T cell differentiation, survival and activation. Zamoyska R, Basson A, Filby A, Legname G, Lovatt M, Seddon B, Immunol Rev 2003 191 107 118 10.1034/j.1600-065X.2003. 00015.x 12614355
109. HIV-1 Nef interferes with host cell motility by deregulation of Cofilin. Stolp B, Reichman-Fried M, Abraham L, Pan X, Giese SI, Hannemann S, Goulimari P, Raz E, Grosse R, Fackler OT, Cell Host Microbe 2009 6 174 186 10.1016/j.chom.2009.06.004 19683683
110. HIV-1 Nef Limits Communication between Linker of Activated T Cells and SLP-76 To Reduce Formation of SLP-76-Signaling Microclusters following TCR Stimulation. Abraham L, Bankhead P, Pan X, Engel U, Fackler OT, J Immunol 2012 189 1898 1910 10.4049/jimmunol.1200652 22802418
111. Uncoordinated 119 protein controls trafficking of Lck via the Rab11 endosome and is critical for immunological synapse formation. Gorska MM, Liang Q, Karim Z, Alam R, J Immunol 2009 183 1675 1684 10.4049/jimmunol.0900792 19592652
112. The human immunodeficiency virus-1 nef gene product: a positive factor for viral infection and replication in primary lymphocytes and macrophages. Miller MD, Warmerdam MT, Gaston I, Greene WC, Feinberg MB, J Exp Med 1994 179 101 113 10.1084/jem.179.1.101 8270859
113. The importance of nef in the induction of human immunodeficiency virus type 1 replication from primary quiescent CD4 lymphocytes. Spina CA, Kwoh TJ, Chowers MY, Guatelli JC, Richman DD, J Exp Med 1994 179 115 123 10.1084/jem.179.1.115 7903679
114. Regulation of HIV-1 latency by T-cell activation. Williams SA, Greene WC, Cytokine 2007 39 63 74 10.1016/j.cyto.2007.05.017 17643313
115. Massive secretion by T cells is caused by HIV Nef in infected cells and by Nef transfer to bystander cells. Muratori C, Cavallin LE, Kratzel K, Tinari A, De Milito A, Fais S, D'Aloja P, Federico M, Vullo V, Fomina A, et al. Cell Host Microbe 2009 6 218 230 10.1016/j.chom.2009.06.009 19748464
116. HIV Nef is secreted in exosomes and triggers apoptosis in bystander CD4+ T cells. Lenassi M, Cagney G, Liao M, Vaupotic T, Bartholomeeusen K, Cheng Y, Krogan NJ, Plemenitas A, Peterlin BM, Traffic 2010 11 110 122 10.1111/j.1600-0854.2009.01006.x 19912576
117. HIV-1 Nef mimics an integrin receptor signal that recruits the polycomb group protein Eed to the plasma membrane. Witte V, Laffert B, Rosorius O, Lischka P, Blume K, Galler G, Stilper A, Willbold D, D'Aloja P, Sixt M, et al. Mol Cell 2004 13 179 190 10.1016/S1097-2765(04)00004-8 14759364
118. Nef enhances human immunodeficiency virus replication and responsiveness to interleukin-2 in human lymphoid tissue ex vivo. Glushakova S, Grivel JC, Suryanarayana K, Meylan P, Lifson JD, Desrosiers R, Margolis L, J Virol 1999 73 3968 3974 10196292
119. CD4 down-modulation by human immunodeficiency virus type 1 Nef correlates with the efficiency of viral replication and with CD4(+) T-cell depletion in human lymphoid tissue ex vivo. Glushakova S, Munch J, Carl S, Greenough TC, Sullivan JL, Margolis L, Kirchhoff F, J Virol 2001 75 10113 10117 10.1128/JVI.75.21.10113-10117.2001 11581379
120. Determinants in HIV-1 Nef for enhancement of virus replication and depletion of CD4+ T lymphocytes in human lymphoid tissue ex vivo. Homann S, Tibroni N, Baumann I, Sertel S, Keppler OT, Fackler OT, Retrovirology 2009 6 6 10.1186/1742-4690-6-6 19146681
121. Nef functions in BLT mice to enhance HIV-1 replication and deplete CD4+CD8+ thymocytes. Zou W, Denton PW, Watkins RL, Krisko JF, Nochi T, Foster JL, Garcia JV, Retrovirology 2012 9 44 10.1186/1742-4690-9-44 22640559
122. Dynamics of subsynaptic vesicles and surface microclusters at the immunological synapse. Purbhoo MA, Liu H, Oddos S, Owen DM, Neil MA, Pageon SV, French PM, Rudd CE, Davis DM, Sci Signal 2010 3 a36 10.1126/scisignal.2000645 20460647
123. Pre-existing clusters of the adaptor Lat do not participate in early T cell signaling events. Williamson DJ, Owen DM, Rossy J, Magenau A, Wehrmann M, Gooding JJ, Gaus K, Nat Immunol 2011 12 655 662 10.1038/ni.2049 21642986
124. Inhibition of T-cell receptor signal transduction and viral expression by the linker for activation of T cells-interacting p12(I) protein of human T-cell leukemia/lymphoma virus type 1. Fukumoto R, Dundr M, Nicot C, Adams A, Valeri VW, Samelson LE, Franchini G, J Virol 2007 81 9088 9099 10.1128/JVI.02703-06 17582004
125. The adaptor molecules LAT and SLP-76 are specifically targeted by Yersinia to inhibit T cell activation. Gerke C, Falkow S, Chien YH, J Exp Med 2005 201 361 371 10.1084/jem.20041120 15699071
126. Modulation of T-cell receptor signal transduction by herpesvirus signaling adaptor protein. Lee SH, Chung YH, Cho NH, Gwack Y, Feng P, Jung JU, Mol Cell Biol 2004 24 5369 5382 10.1128/MCB.24.12.5369-5382.2004 15169900