Mutation of a diacidic motif in SIV-PBj Nef impairs T-cell activation and enteropathic disease

Retrovirology

Volumn 8, Issue , 2011, Pages

  Tschulena, Ulrich ^a   Sanzenbacher, Ralf ^a   Mühlebach, Michael D ^a   Berger, André ^a   Münch, Jan ^b   Schindler, Michael ^c   Kirchhoff, Frank ^b   Plesker, Roland ^a   Coulibaly, Cheick ^a   Panitz, Sylvia ^a   Prüfer, Steffen ^a   Muckenfuss, Heide ^a   Hamdorf, Matthias ^a   Schweizer, Matthias ^a   Cichutek, Klaus ^a   Flory, Egbert ^a  

^a PAUL EHRLICH INSTITUT   (Germany)

^b UNIVERSITY OF ULM   (Germany)

^c LEIBNIZ INSTITUTE FOR EXPERIMENTAL VIROLOGY   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

CD28 ANTIGEN; CD4 ANTIGEN; INTERLEUKIN 2; MITOGEN ACTIVATED PROTEIN KINASE; MITOGEN ACTIVATED PROTEIN KINASE 1; NEF PROTEIN; RAF PROTEIN;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CONTROLLED STUDY; DOWN REGULATION; ENTEROPATHY; GENE MUTATION; HUMAN; HUMAN CELL; IMMUNOMODULATION; IN VITRO STUDY; IN VIVO STUDY; INTESTINE LYMPHATIC TISSUE; LYMPHOCYTE PROLIFERATION; MACACA; NONHUMAN; PERIPHERAL BLOOD MONONUCLEAR CELL; PHENOTYPE; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN MOTIF; SIGNAL TRANSDUCTION; SIMIAN IMMUNODEFICIENCY VIRUS; T LYMPHOCYTE ACTIVATION; VIRUS LOAD; VIRUS REPLICATION; WILD TYPE; ANIMAL; CELL CULTURE; CHEMISTRY; COLON; GENETICS; IMMUNOLOGY; LYMPHOCYTE ACTIVATION; LYMPHOCYTOPENIA; MACACA NEMESTRINA; METABOLISM; MONKEY DISEASE; MUTATION; PATHOGENICITY; PATHOLOGY; PATHOPHYSIOLOGY; SIMIAN ACQUIRED IMMUNODEFICIENCY SYNDROME; T LYMPHOCYTE; VIREMIA; VIROLOGY;

ANIMALIA; LENTIVIRUS; MACACA NEMESTRINA; SIMIAN IMMUNODEFICIENCY VIRUS;

AMINO ACID MOTIFS; ANIMALS; CELLS, CULTURED; COLON; GENE PRODUCTS, NEF; HUMANS; LYMPHOCYTE ACTIVATION; LYMPHOPENIA; MACACA NEMESTRINA; MONKEY DISEASES; MUTATION; PHENOTYPE; SIMIAN ACQUIRED IMMUNODEFICIENCY SYNDROME; SIMIAN IMMUNODEFICIENCY VIRUS; T-LYMPHOCYTES; VIREMIA; VIRUS REPLICATION;

EID: 79952734877     PISSN: None     EISSN: 17424690     Source Type: Journal    
DOI: 10.1186/1742-4690-8-14     Document Type: Article

References (71)

1. Clark SJ, Saag MS, Decker WD, Campbell-Hill S, Roberson JL, Veldkamp PJ, Kappes JC, Hahn BH, Shaw GM. High titers of cytopathic virus in plasma of patients with symptomatic primary HIV-1 infection. N Engl J Med 1991, 324:954-60. 10.1056/NEJM199104043241404, 1900576.
2. Daar ES, Moudgil T, Meyer RD, Ho DD. Transient high levels of viremia in patients with primary human immunodeficiency virus type 1 infection. N Engl J Med 1991, 324:961-4. 10.1056/NEJM199104043241405, 1823118.
3. Farthing C, Gazzard B. Acute illnesses associated with HTLV-III seroconversion. Lancet 1985, 1:935-6. 10.1016/S0140-6736(85)91715-5, 2858784.
4. Haase AT. Perils at mucosal front lines for HIV and SIV and their hosts. Nat Rev Immunol 2005, 5:783-792.
5. Li Q, Duan L, Estes JD, Ma ZM, Rourke T, Wang Y, Reilly C, Carlis J, Miller CJ, Haase AT. Peak SIV replication in resting memory CD4+ T cells depletes gut lamina propria CD4+ T cells. Nature 2005, 434:1148-1152.
6. Brenchley JM, Schacker TW, Ruff LE, Price DA, Taylor JH, Beilman GJ, Nguyen PL, Khoruts A, Larson M, Haase AT, et al. CD4+ T cell depletion during all stages of HIV disease occurs predominantly in the gastrointestinal tract. J Exp Med 2004, 200:749-759. 10.1084/jem.20040874, 2211962, 15365096.
7. Mehandru S, Poles MA, Tenner-Racz K, Horowitz A, Hurley A, Hogan C, Boden D, Racz P, Markowitz M. Primary HIV-1 infection is associated with preferential depletion of CD4+ T lymphocytes from effector sites in the gastrointestinal tract. J Exp Med 2004, 200:761-770. 10.1084/jem.20041196, 2211967, 15365095.
8. Veazey RS, DeMaria M, Chalifoux LV, Shvetz DE, Pauley DR, Knight HL, Rosenzweig M, Johnson RP, Desrosiers RC, Lackner AA. Gastrointestinal tract as a major site of CD4+ T cell depletion and viral replication in SIV infection. Science 1998, 280:427-431. 10.1126/science.280.5362.427, 9545219.
9. Gordon SN, Klatt NR, Bosinger SE, Brenchley JM, Milush JM, Engram JC, Dunham RM, Paiardini M, Klucking S, Danesh A, et al. Severe depletion of mucosal CD4+ T cells in AIDS-free simian immunodeficiency virus-infected sooty mangabeys. J Immunol 2007, 179:3026-3034. 2365740, 17709517.
10. Pandrea IV, Gautam R, Ribeiro RM, Brenchley JM, Butler IF, Pattison M, Rasmussen T, Marx PA, Silvestri G, Lackner AA, et al. Acute loss of intestinal CD4+ T cells is not predictive of simian immunodeficiency virus virulence. J Immunol 2007, 179:3035-3046. 2367134, 17709518.
11. Brenchley JM, Price DA, Schacker TW, Asher TE, Silvestri G, Rao S, Kazzaz Z, Bornstein E, Lambotte O, Altmann D, et al. Microbial translocation is a cause of systemic immune activation in chronic HIV infection. Nat Med 2006, 12:1365-1371. 10.1038/nm1511, 17115046.
12. Brenchley JM, Price DA, Douek DC. HIV disease: fallout from a mucosal catastrophe?. Nat Immunol 2006, 7:235-239. 10.1038/ni1316, 16482171.
13. Silvestri G, Sodora DL, Koup RA, Paiardini M, O'Neil SP, McClure HM, Staprans SI, Feinberg MB. Nonpathogenic SIV infection of sooty mangabeys is characterized by limited bystander immunopathology despite chronic high-level viremia. Immunity 2003, 18:441-452. 10.1016/S1074-7613(03)00060-8, 12648460.
14. Mattapallil JJ, Douek DC, Hill B, Nishimura Y, Martin M, Roederer M. Massive infection and loss of memory CD4+ T cells in multiple tissues during acute SIV infection. Nature 2005, 434:1093-1097. 10.1038/nature03501, 15793563.
15. Dewhurst S, Embretson JE, Anderson DC, Mullins JI, Fultz PN. Sequence analysis and acute pathogenicity of molecularly cloned SIVSMM-PBj14. Nature 1990, 345:636-40. 10.1038/345636a0, 1971917.
16. Fultz PN. Replication of an acutely lethal simian immunodeficiency virus activates and induces proliferation of lymphocytes. J Virol 1991, 65:4902-9. 248951, 1870205.
17. McClure HM, Anderson DC, Fultz PN, Ansari AA, Lockwood E, Brodie A. Spectrum of disease in macaque monkeys chronically infected with SIV/SMM. Vet Immunol Immunopathol 1989, 21:13-24. 10.1016/0165-2427(89)90126-8, 2570479.
18. Fultz PN. SIVsmmPBj14: an atypical lentivirus. Curr Top Microbiol Immunol 1994, 188:65-76.
19. Kapembwa MS, Batman PA, Fleming SC, Griffin GE. HIV enteropathy. Lancet 1989, 2:1521-2. 10.1016/S0140-6736(89)92961-9, 2574790.
20. Sharpstone D, Gazzard B. Gastrointestinal manifestations of HIV infection. Lancet 1996, 348:379-83. 10.1016/S0140-6736(96)01034-3, 8709738.
21. Birx DL, Lewis MG, Vahey M, Tencer K, Zack PM, Brown CR, Jahrling PB, Tosato G, Burke D, Redfield R. Association of interleukin-6 in the pathogenesis of acutely fatal SIVsmm/PBj-14 in pigtailed macaques. AIDS Res Hum Retroviruses 1993, 9:1123-9. 10.1089/aid.1993.9.1123, 8312054.
22. Schwiebert R, Fultz PN. Immune activation and viral burden in acute disease induced by simian immunodeficiency virus SIVsmmPBj14: correlation between in vitro and in vivo events. J Virol 1994, 68:5538-47. 236954, 8057436.
23. Fultz PN, Zack PM. Unique lentivirus--host interactions: SIVsmmPBj14 infection of macaques. Virus Res 1994, 32:205-225. 10.1016/0168-1702(94)90042-6, 8067054.
24. Novembre FJ, Johnson PR, Lewis MG, Anderson DC, Klumpp S, McClure HM, Hirsch VM. Multiple viral determinants contribute to pathogenicity of the acutely lethal simian immunodeficiency virus SIVsmmPBj variant. J Virol 1993, 67:2466-74. 237565, 8474153.
25. Saucier M, Hodge S, Dewhurst S, Gibson T, Gibson JP, McClure HM, Novembre FJ. The tyrosine-17 residue of Nef in SIVsmmPBj14 is required for acute pathogenesis and contributes to replication in macrophages. Virology 1998, 244:261-72. 10.1006/viro.1998.9133, 9601497.
26. Luo W, Peterlin BM. Activation of the T-cell receptor signaling pathway by Nef from an aggressive strain of simian immunodeficiency virus. J Virol 1997, 71:9531-9537. 230260, 9371616.
27. Du Z, Lang SM, Sasseville VG, Lackner AA, Ilyinskii PO, Daniel MD, Jung JU, Desrosiers RC. Identification of a nef allele that causes lymphocyte activation and acute disease in macaque monkeys. Cell 1995, 82:665-74. 10.1016/0092-8674(95)90038-1, 7664345.
28. Du Z, Ilyinskii PO, Sasseville VG, Newstein M, Lackner AA, Desrosiers RC. Requirements for lymphocyte activation by unusual strains of simian immunodeficiency virus. J Virol 1996, 70:4157-61. 190308, 8648760.
29. Sasseville VG, Du Z, Chalifoux LV, Pauley DR, Young HL, Sehgal PK, Desrosiers RC, Lackner AA. Induction of lymphocyte proliferation and severe gastrointestinal disease in macaques by a nef gene variant SIVmac239. Am J Pathol 1996, 149:163-176. 1865222, 8686740.
30. Dehghani H, Brown CR, Plishka R, Buckler-White A, Hirsch VM. The ITAM in Nef influences acute pathogenesis of AIDS-inducing simian immunodeficiency viruses SIVsm and SIVagm without altering kinetics or extent of viremia. J Virol 2002, 76:4379-89. 10.1128/JVI.76.9.4379-4389.2002, 155068, 11932405.
31. Wagener S, Dittmar MT, Beer B, Konig R, Plesker R, Norley S, Kurth R, Cichutek K. The U3 promoter and the nef gene of simian immunodeficiency virus (SIV) smmPBj1.9 do not confer acute pathogenicity upon SIVagm. J Virol 1998, 72:3446-50. 109849, 9525679.
32. Kestler HW, Ringler DJ, Mori K, Panicali DL, Sehgal PK, Daniel MD, Desrosiers RC. Importance of the nef gene for maintenance of high virus loads and for development of AIDS. Cell 1991, 65:651-62. 10.1016/0092-8674(91)90097-I, 2032289.
33. Schindler M, Munch J, Kutsch O, Li H, Santiago ML, Bibollet-Ruche F, Muller-Trutwin MC, Novembre FJ, Peeters M, Courgnaud V, et al. Nef-mediated suppression of T cell activation was lost in a lentiviral lineage that gave rise to HIV-1. Cell 2006, 125:1055-1067. 10.1016/j.cell.2006.04.033, 16777597.
34. Schindler M, Schmokel J, Specht A, Li H, Munch J, Khalid M, Sodora DL, Hahn BH, Silvestri G, Kirchhoff F. Inefficient Nef-mediated downmodulation of CD3 and MHC-I correlates with loss of CD4+T cells in natural SIV infection. PLoS Pathog 2008, 4:e1000107. 10.1371/journal.ppat.1000107, 2444047, 18636106.
35. Aiken C, Konner J, Landau NR, Lenburg ME, Trono D. Nef induces CD4 endocytosis: requirement for a critical dileucine motif in the membrane-proximal CD4 cytoplasmic domain. Cell 1994, 76:853-64. 10.1016/0092-8674(94)90360-3, 8124721.
36. Fackler OT, Alcover A, Schwartz O. Modulation of the immunological synapse: a key to HIV-1 pathogenesis?. Nat Rev Immunol 2007, 7:310-317. 10.1038/nri2041, 17380160.
37. Iafrate AJ, Bronson S, Skowronski J. Separable functions of Nef disrupt two aspects of T cell receptor machinery: CD4 expression and CD3 signaling. EMBO J 1997, 16:673-684. 10.1093/emboj/16.4.673, 1169669, 9049297.
38. Schwartz O, Marechal V, Le Gall S, Lemonnier F, Heard JM. Endocytosis of major histocompatibility complex class I molecules is induced by the HIV-1 Nef protein. Nat Med 1996, 2:338-42. 10.1038/nm0396-338, 8612235.
39. Schrager JA, Der Minassian V, Marsh JW. HIV Nef increases T cell ERK MAP kinase activity. J Biol Chem 2002, 277:6137-42. 10.1074/jbc.M107322200, 11726657.
40. Hodge DR, Dunn KJ, Pei GK, Chakrabarty MK, Heidecker G, Lautenberger JA, Samuel KP. Binding of c-Raf1 kinase to a conserved acidic sequence within the carboxyl-terminal region of the HIV-1 Nef protein. J Biol Chem 1998, 273:15727-33. 10.1074/jbc.273.25.15727, 9624170.
41. Daum G, Eisenmann-Tappe I, Fries HW, Troppmair J, Rapp UR. The ins and outs of Raf kinases. Trends Biochem Sci 1994, 19:474-80. 10.1016/0968-0004(94)90133-3, 7855890.
42. Avots A, Hoffmeyer A, Flory E, Cimanis A, Rapp UR, Serfling E. GABP factors bind to a distal interleukin 2 (IL-2) enhancer and contribute to c-Raf-mediated increase in IL-2 induction. Mol Cell Biol 1997, 17:4381-9. 232292, 9234696.
43. Perez OD, Mitchell D, Jager GC, South S, Murriel C, McBride J, Herzenberg LA, Kinoshita S, Nolan GP. Leukocyte functional antigen 1 lowers T cell activation thresholds and signaling through cytohesin-1 and Jun-activating binding protein 1. Nat Immunol 2003, 4:1083-92. 10.1038/ni984, 14528303.
44. Taylor-Fishwick DA, Siegel JN. Raf-1 provides a dominant but not exclusive signal for the induction of CD69 expression on T cells. Eur J Immunol 1995, 25:3215-21. 10.1002/eji.1830251203, 8566003.
45. Flory E, Weber CK, Chen P, Hoffmeyer A, Jassoy C, Rapp UR. Plasma membrane-targeted Raf kinase activates NF-kappaB and human immunodeficiency virus type 1 replication in T lymphocytes. J Virol 1998, 72:2788-94. 109723, 9525598.
46. Flory E, Hoffmeyer A, Smola U, Rapp UR, Bruder JT. Raf-1 kinase targets GA-binding protein in transcriptional regulation of the human immunodeficiency virus type 1 promoter. J Virol 1996, 70:2260-8. 190067, 8642652.
47. Hemonnot B, Cartier C, Gay B, Rebuffat S, Bardy M, Devaux C, Boyer V, Briant L. The host cell MAP kinase ERK-2 regulates viral assembly and release by phosphorylating the p6gag protein of HIV-1. J Biol Chem 2004, 279:32426-32434. 10.1074/jbc.M313137200, 15155723.
48. Ylisastigui L, Kaur R, Johnson H, Volker J, He G, Hansen U, Margolis D. Mitogen-activated protein kinases regulate LSF occupancy at the human immunodeficiency virus type 1 promoter. J Virol 2005, 79:5952-5962. 10.1128/JVI.79.10.5952-5962.2005, 1091734, 15857981.
49. Collette Y, Dutartre H, Benziane A, Ramos M, Benarous R, Harris M, Olive D. Physical and functional interaction of Nef with Lck. HIV-1 Nef-induced T-cell signaling defects. J Biol Chem 1996, 271:6333-6341. 10.1074/jbc.271.11.6333, 8626429.
50. Iafrate AJ, Carl S, Bronson S, Stahl-Hennig C, Swigut T, Skowronski J, Kirchhoff F. Disrupting surfaces of nef required for downregulation of CD4 and for enhancement of virion infectivity attenuates simian immunodeficiency virus replication in vivo. J Virol 2000, 74:9836-9844. 10.1128/JVI.74.21.9836-9844.2000, 102020, 11024110.
51. Lindwasser OW, Smith WJ, Chaudhuri R, Yang P, Hurley JH, Bonifacino JS. A diacidic motif in human immunodeficiency virus type 1 Nef is a novel determinant of binding to AP-2. J Virol 2008, 82:1166-1174. 10.1128/JVI.01874-07, 2224420, 18032517.
52. Geyer M, Yu H, Mandic R, Linnemann T, Zheng YH, Fackler OT, Peterlin BM. Subunit H of the V-ATPase binds to the medium chain of adaptor protein complex 2 and connects Nef to the endocytic machinery. J Biol Chem 2002, 277:28521-28529. 10.1074/jbc.M200522200, 12032142.
53. Lu X, Yu H, Liu SH, Brodsky FM, Peterlin BM. Interactions between HIV1 Nef and vacuolar ATPase facilitate the internalization of CD4. Immunity 1998, 8:647-56. 10.1016/S1074-7613(00)80569-5, 9620685.
54. Grossman Z, Meier-Schellersheim M, Paul WE, Picker LJ. Pathogenesis of HIV infection: what the virus spares is as important as what it destroys. Nat Med 2006, 12:289-295. 10.1038/nm1380, 16520776.
55. Sodora DL, Silvestri G. Immune activation and AIDS pathogenesis. Aids 2008, 22:439-446. 10.1097/QAD.0b013e3282f2dbe7, 18301056.
56. Owaki H, Varma R, Gillis B, Bruder JT, Rapp UR, Davis LS, Geppert TD. Raf-1 is required for T cell IL2 production. Embo J 1993, 12:4367-73. 413733, 8223446.
57. Lock M, Greenberg ME, Iafrate AJ, Swigut T, Muench J, Kirchhoff F, Shohdy N, Skowronski J. Two elements target SIV Nef to the AP-2 clathrin adaptor complex, but only one is required for the induction of CD4 endocytosis. EMBO J 1999, 18:2722-2733. 10.1093/emboj/18.10.2722, 1171354, 10329619.
58. Swigut T, Shohdy N, Skowronski J. Mechanism for down-regulation of CD28 by Nef. Embo J 2001, 20:1593-604. 10.1093/emboj/20.7.1593, 145469, 11285224.
59. Robertson SE, Setty SR, Sitaram A, Marks MS, Lewis RE, Chou MM. Extracellular signal-regulated kinase regulates clathrin-independent endosomal trafficking. Mol Biol Cell 2006, 17:645-657. 10.1091/mbc.E05-07-0662, 1356576, 16314390.
60. Giorgi JV, Hultin LE, McKeating JA, Johnson TD, Owens B, Jacobson LP, Shih R, Lewis J, Wiley DJ, Phair JP, et al. Shorter survival in advanced human immunodeficiency virus type 1 infection is more closely associated with T lymphocyte activation than with plasma virus burden or virus chemokine coreceptor usage. J Infect Dis 1999, 179:859-870. 10.1086/314660, 10068581.
61. Sousa AE, Carneiro J, Meier-Schellersheim M, Grossman Z, Victorino RM. CD4 T cell depletion is linked directly to immune activation in the pathogenesis of HIV-1 and HIV-2 but only indirectly to the viral load. J Immunol 2002, 169:3400-3406.
62. Pandrea I, Gaufin T, Brenchley JM, Gautam R, Monjure C, Gautam A, Coleman C, Lackner AA, Ribeiro RM, Douek DC, et al. Cutting edge: Experimentally induced immune activation in natural hosts of simian immunodeficiency virus induces significant increases in viral replication and CD4+ T cell depletion. J Immunol 2008, 181:6687-6691. 2695139, 18981083.
63. Kaur A, Grant RM, Means RE, McClure H, Feinberg M, Johnson RP. Diverse host responses and outcomes following simian immunodeficiency virus SIVmac239 infection in sooty mangabeys and rhesus macaques. J Virol 1998, 72:9597-9611. 110469, 9811693.
64. Pandrea I, Sodora DL, Silvestri G, Apetrei C. Into the wild: simian immunodeficiency virus (SIV) infection in natural hosts. Trends Immunol 2008, 29:419-428. 10.1016/j.it.2008.05.004, 2840226, 18676179.
65. Klatt NR, Harris LD, Vinton CL, Sung H, Briant JA, Tabb B, Morcock D, McGinty JW, Lifson JD, Lafont BA, et al. Compromised gastrointestinal integrity in pigtail macaques is associated with increased microbial translocation, immune activation, and IL-17 production in the absence of SIV infection. Mucosal Immunol 2010, 3:387-398. 10.1038/mi.2010.14, 2891168, 20357762.
66. Fultz PN, McClure HM, Anderson DC, Switzer WM. Identification and biologic characterization of an acutely lethal variant of simian immunodeficiency virus from sooty mangabeys (SIV/SMM). AIDS Res Hum Retroviruses 1989, 5:397-409. 10.1089/aid.1989.5.397, 2765298.
67. Muhlebach MD, Wolfrum N, Schule S, Tschulena U, Sanzenbacher R, Flory E, Cichutek K, Schweizer M. Stable transduction of primary human monocytes by simian lentiviral vector PBj. Mol Ther 2005, 12:1206-1216. 10.1016/j.ymthe.2005.06.483, 16150648.
68. Sanzenbacher R, Kabelitz D, Janssen O. SLP-76 binding to p56lck: a role for SLP-76 in CD4-induced desensitization of the TCR/CD3 signaling complex. J Immunol 1999, 163:3143-52.
69. Muckenfuss H, Kaiser JK, Krebil E, Battenberg M, Schwer C, Cichutek K, Munk C, Flory E. Sp1 and Sp3 regulate basal transcription of the human APOBEC3G gene. Nucleic Acids Res 2007, 35:3784-3796. 10.1093/nar/gkm340, 1920263, 17517765.
70. Kirchhoff F, Schindler M, Bailer N, Renkema GH, Saksela K, Knoop V, Muller-Trutwin MC, Santiago ML, Bibollet-Ruche F, Dittmar MT, et al. Nef proteins from simian immunodeficiency virus-infected chimpanzees interact with p21-activated kinase 2 and modulate cell surface expression of various human receptors. J Virol 2004, 78:6864-6874. 10.1128/JVI.78.13.6864-6874.2004, 421647, 15194762.
71. Schindler M, Wurfl S, Benaroch P, Greenough TC, Daniels R, Easterbrook P, Brenner M, Munch J, Kirchhoff F. Down-modulation of mature major histocompatibility complex class II and up-regulation of invariant chain cell surface expression are well-conserved functions of human and simian immunodeficiency virus nef alleles. J Virol 2003, 77:10548-10556. 10.1128/JVI.77.19.10548-10556.2003, 228419, 12970439.