HIV-1 Tat protein induces production of proinflammatory cytokines by human dendritic cells and monocytes/macrophages through engagement of TLR4-MD2-CD14 complex and activation of NF-κB pathway

PLoS ONE

Volumn 10, Issue 6, 2015, Pages

  Haij, Nawal Ben ^a,b,c   Planès, Rémi ^a,b,c   Leghmari, Kaoutar ^a,b,c   Serrero, Manutea ^a,b,c   Delobel, Pierre ^a,b,c   Izopet, Jacques ^a,b,c   BenMohamed, Lbachir ^d   Bahraoui, Elmostafa ^a,b,c  

^a CNRS   (France)

^b UNIVERSITÉ DE TOULOUSE   (France)

^c TOULOUSE UNIVERSITY HOSPITAL   (France)

^d UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CD14 ANTIGEN; CXCL1 CHEMOKINE; CYTOKINE; DYNAMIN; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERLEUKIN 6; INTERLEUKIN 8; PROTEIN MD 2; SUPPRESSOR OF CYTOKINE SIGNALING 1; TOLL LIKE RECEPTOR 4; TRANSACTIVATOR PROTEIN; AUTACOID; MULTIPROTEIN COMPLEX; PROTEIN BINDING; SOCS1 PROTEIN, HUMAN; SUPPRESSOR OF CYTOKINE SIGNALING;

ANIMAL CELL; ARTICLE; BONE MARROW CELL; CELL SURFACE; CONTROLLED STUDY; CYTOKINE PRODUCTION; DENDRITIC CELL; DOWN REGULATION; EMBRYO; ENDOCYTOSIS; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS 1 INFECTION; LIPID RAFT; MONOCYTE; MOUSE; NONHUMAN; PERITONEUM MACROPHAGE; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN PROTEIN INTERACTION; ANIMAL; CELL LINE; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; IMMUNOLOGY; MACROPHAGE; METABOLISM; SIGNAL TRANSDUCTION; VIROLOGY;

HUMAN IMMUNODEFICIENCY VIRUS 1; MURINAE; MUS;

ANIMALS; ANTIGENS, CD14; CELL LINE; CYTOKINES; DENDRITIC CELLS; DYNAMINS; ENDOCYTOSIS; HIV INFECTIONS; HUMANS; INFLAMMATION MEDIATORS; LYMPHOCYTE ANTIGEN 96; MACROPHAGES; MACROPHAGES, PERITONEAL; MICE; MONOCYTES; MULTIPROTEIN COMPLEXES; NF-KAPPA B; PROTEIN BINDING; SIGNAL TRANSDUCTION; SUPPRESSOR OF CYTOKINE SIGNALING 1 PROTEIN; SUPPRESSOR OF CYTOKINE SIGNALING PROTEINS; TAT GENE PRODUCTS, HUMAN IMMUNODEFICIENCY VIRUS; TOLL-LIKE RECEPTOR 4;

EID: 84939213978     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0129425     Document Type: Article

References (115)

1. Clerici M, Wynn TA, Berzofsky JA, Blatt SP, Hendrix CW, et al. (1994) Role of interleukin-10 in T helper cell dysfunction in asymptomatic individuals infected with the human immunodeficiency virus. J Clin Invest 93: 768-775. PMID: 8113410.
2. Brockman MA, Kwon DS, Tighe DP, Pavlik DF, Rosato PC, et al. (2009) IL-10 is up-regulated in multiple cell types during viremic HIV infection and reversibly inhibits virus-specific T cells. Blood 114: 346-356. doi:10.1182/blood-2008-12-191296 PMID: 19365081.
3. Day CL, Kaufmann DE, Kiepiela P, Brown JA, Moodley ES, et al. (2006) PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression. Nature 443: 350-354. PMID: 16921384.
4. Trautmann L, Janbazian L, Chomont N, Said EA, Gimmig S, et al. (2006) Upregulation of PD-1 expression on HIV-specific CD8+ T cells leads to reversible immune dysfunction. Nat Med 12: 1198- 1202. PMID: 16917489.
5. Wang X, Zhang Z, Zhang S, Fu J, Yao J, et al. (2008) B7-H1 up-regulation impairs myeloid DC and correlates with disease progression in chronic HIV-1 infection. Eur J Immunol 38: 3226-3236. doi:10.1002/eji.200838285 PMID: 18924219.
6. Favre D, Mold J, Hunt PW, Kanwar B, Loke P, et al. Tryptophan catabolism by indoleamine 2, 3-dioxygenase 1 alters the balance of TH17 to regulatory T cells in HIV disease. Sci Transl Med 2: 32ra36. doi:10.1126/scitranslmed.3000632 PMID: 20484731.
7. Appay V, Sauce D (2008) Immune activation and inflammation in HIV-1 infection: causes and consequences. J Pathol 214: 231-241. PMID: 18161758.
8. Spudich S, Gonzalez-Scarano F (2012) HIV-1-related central nervous system disease: current issues in pathogenesis, diagnosis, and treatment. Cold Spring Harb Perspect Med 2: A007120. doi:10.1101/cshperspect.a007120 PMID: 22675662.
9. Aoki Y, Tosato G (2003) Viral and cellular cytokines as therapeutic targets in AIDS-related lymphoproliferative disorders. Curr Drug Targets Cardiovasc Haematol Disord 3: 81-96. PMID: 12769647.
10. Aoki Y, Tosato G (2004) HIV-1 Tat enhances Kaposi sarcoma-associated herpesvirus (KSHV) infectivity. Blood 104: 810-814. PMID: 15073028.
11. Orrenius S, Zhivotovsky B, Nicotera P (2003) Regulation of cell death: The calcium-apoptosis link. Nat Rev Mol Cell Biol 4: 552-565. PMID: 12838338.
12. Breen EC (2002) Pro- And anti-inflammatory cytokines in human immunodeficiency virus infection and acquired immunodeficiency syndrome. Pharmacol Ther 95: 295-304. PMID: 12243799.
13. Brenchley JM, Price DA, Schacker TW, Asher TE, Silvestri G, et al. (2006) Microbial translocation is a cause of systemic immune activation in chronic HIV infection. Nat Med 12: 1365-1371. PMID: 17115046.
14. Clerici M, Villa ML, Shearer GM (1994) The role of cytokines in immune response to HIV. Acta Microbiol Immunol Hung 41 Suppl: 5-10. PMID: 7915617.
15. Barillari G, Gendelman R, Gallo RC, Ensoli B (1993) The Tat protein of human immunodeficiency virus type 1, a growth factor for AIDS Kaposi sarcoma and cytokine-activated vascular cells, induces adhesion of the same cell types by using integrin receptors recognizing the RGD amino acid sequence. Proc Natl Acad Sci U S A 90: 7941-7945. PMID: 7690138.
16. Poli G, Fauci AS (1992) The role of monocyte/macrophages and cytokines in the pathogenesis of HIV infection. Pathobiology 60: 246-251. PMID: 1388722.
17. Keating SM, Jacobs ES, Norris PJ (2012) Soluble mediators of inflammation in HIV and their implications for therapeutics and vaccine development. Cytokine Growth Factor Rev 23: 193-206. doi:10.1016/j.cytogfr.2012.05.006 PMID: 22743035.
18. Ameglio F, Capobianchi MR, Castilletti C, Cordiali Fei P, Fais S, et al. (1994) Recombinant gp120 induces IL-10 in resting peripheral blood mononuclear cells; correlation with the induction of other cytokines. Clin Exp Immunol 95: 455-458. PMID: 7511078.
19. Shan M, Klasse PJ, Banerjee K, Dey AK, Iyer SP, et al. (2007) HIV-1 gp120 mannoses induce immunosuppressive responses from dendritic cells. PLoS Pathog 3: E169. PMID: 17983270.
20. Williams MA, Trout R, Spector SA (2002) HIV-1 gp120 modulates the immunological function and expression of accessory and co-stimulatory molecules of monocyte-derived dendritic cells. J Hematother Stem Cell Res 11: 829-847. PMID: 12427289.
21. Martinson JA, Montoya CJ, Usuga X, Ronquillo R, Landay AL, et al. (2010) Chloroquine modulates HIV-1-induced plasmacytoid dendritic cell alpha interferon: Implication for T-cell activation. Antimicrob Agents Chemother 54: 871-881. doi:10.1128/AAC.01246-09 PMID: 19949061.
22. Badou A, Bennasser Y, Moreau M, Leclerc C, Benkirane M, et al. (2000) Tat protein of human immunodeficiency virus type 1 induces interleukin-10 in human peripheral blood monocytes: Implication of protein kinase C-dependent pathway. J Virol 74: 10551-10562. PMID: 11044099.
23. Buonaguro L, Barillari G, Chang HK, Bohan CA, Kao V, et al. (1992) Effects of the human immunodeficiency virus type 1 Tat protein on the expression of inflammatory cytokines. J Virol 66: 7159-7167. PMID: 1279199.
24. Gandhi N, Saiyed Z, Thangavel S, Rodriguez J, Rao KV, et al. (2009) Differential effects of HIV type 1 clade B and clade C Tat protein on expression of proinflammatory and antiinflammatory cytokines by primary monocytes. AIDS Res Hum Retroviruses 25: 691-699. doi:10.1089/aid.2008.0299 PMID: 19621989.
25. Yang Y, Wu J, Lu Y (2010) Mechanism of HIV-1-TAT induction of interleukin-1beta from human monocytes: Involvement of the phospholipase C/protein kinase C signaling cascade. J Med Virol 82: 735- 746. doi:10.1002/jmv.21720 PMID: 20336759.
26. Brigino E, Haraguchi S, Koutsonikolis A, Cianciolo GJ, Owens U, et al. (1997) Interleukin 10 is induced by recombinant HIV-1 Nef protein involving the calcium/calmodulin-dependent phosphodiesterase signal transduction pathway. Proc Natl Acad Sci U S A 94: 3178-3182. PMID: 9096366.
27. Sarkar R, Mitra D, Chakrabarti S (2013) HIV-1 gp120 protein downregulates Nef induced IL-6 release in immature dentritic cells through interplay of DC-SIGN. PLoS One 8: E59073. doi:10.1371/journal.pone.0059073 PMID: 23554973.
28. Tangsinmankong N, Day NK, Good RA, Haraguchi S (2000) Monocytes are target cells for IL-10 induction by HIV-1 Nef protein. Cytokine 12: 1506-1511. PMID: 11023665.
29. Hoshino S, Konishi M, Mori M, Shimura M, Nishitani C, et al. (2010) HIV-1 Vpr induces TLR4/MyD88- mediated IL-6 production and reactivates viral production from latency. J Leukoc Biol 87: 1133-1143. doi:10.1189/jlb.0809547 PMID: 20145198.
30. Muthumani K, Hwang DS, Choo AY, Mayilvahanan S, Dayes NS, et al. (2005) HIV-1 Vpr inhibits the maturation and activation of macrophages and dendritic cells in vitro. Int Immunol 17: 103-116. PMID: 15611322.
31. Nazli A, Kafka JK, Ferreira VH, Anipindi V, Mueller K, et al. (2013) HIV-1 gp120 induces TLR2- And TLR4-mediated innate immune activation in human female genital epithelium. J Immunol 191: 4246- 4258. doi:10.4049/jimmunol.1301482 PMID: 24043886.
32. Breckpot K, Escors D, Arce F, Lopes L, Karwacz K, et al. (2010) HIV-1 lentiviral vector immunogenicity is mediated by Toll-like receptor 3 (TLR3) and TLR7. J Virol 84: 5627-5636. doi:10.1128/JVI.00014-10 PMID: 20237085.
33. Ben-Haij N, Leghmari K, Planes R, Thieblemont N, Bahraoui E (2013) HIV-1 Tat protein binds to TLR4-MD2 and signals to induce TNF-alpha and IL-10. Retrovirology 10: 123. doi:10.1186/1742-4690-10-123 PMID: 24165011.
34. Beignon AS, McKenna K, Skoberne M, Manches O, DaSilva I, et al. (2005) Endocytosis of HIV-1 activates plasmacytoid dendritic cells via Toll-like receptor-viral RNA interactions. J Clin Invest 115: 3265-3275. PMID: 16224540.
35. Guo H, Gao J, Taxman DJ, Ting JP, Su L (2014) HIV-1 Infection Induces IL-1beta Production via TLR8-Dependent and NLRP3-Inflammasome Mechanisms in Human Monocytes. J Biol Chem.
36. Gringhuis SI, van der Vlist M, van den Berg LM, den Dunnen J, Litjens M, et al. HIV-1 exploits innate signaling by TLR8 and DC-SIGN for productive infection of dendritic cells. Nat Immunol 11: 419-426. doi:10.1038/ni.1858 PMID: 20364151.
37. Berg RK, Melchjorsen J, Rintahaka J, Diget E, Soby S, et al. (2012) Genomic HIV RNA induces innate immune responses through RIG-I-dependent sensing of secondary-structured RNA. PLoS One 7: E29291. doi:10.1371/journal.pone.0029291 PMID: 22235281.
38. Karn J, Stoltzfus CM (2012) Transcriptional and posttranscriptional regulation of HIV-1 gene expression. Cold Spring Harb Perspect Med 2: A006916. doi:10.1101/cshperspect.a006916 PMID: 22355797.
39. Li JC, Yim HC, Lau AS Role of HIV-1 Tat in AIDS pathogenesis: Its effects on cytokine dysregulation and contributions to the pathogenesis of opportunistic infection. Aids 24: 1609-1623. doi:10.1097/QAD.0b013e32833ac6a0 PMID: 20588103.
40. Ott M, Lovett JL, Mueller L, Verdin E (1998) Superinduction of IL-8 in T cells by HIV-1 Tat protein is mediated through NF-kappaB factors. J Immunol 160: 2872-2880. PMID: 9510190.
41. Bennasser Y, Badou A, Tkaczuk J, Bahraoui E (2002) Signaling pathways triggered by HIV-1 Tat in human monocytes to induce TNF-alpha. Virology 303: 174-180. PMID: 12482669.
42. Planes R, BenMohamed L, Leghmari K, Delobel P, Izopet J, et al. (2014) HIV-1 Tat Protein Induces PD-L1 (B7-H1) Expression on Dendritic Cells through Tumor Necrosis Factor Alpha- And Toll-Like Receptor 4-Mediated Mechanisms. J Virol 88: 6672-6689. doi:10.1128/JVI.00825-14PMID: 24696476.
43. Planes R, Bahraoui E (2013) HIV-1 Tat Protein Induces the Production of IDO in Human Monocyte Derived-Dendritic Cells through a Direct Mechanism: Effect on T Cells Proliferation. PLoS One 8: E74551. doi:10.1371/journal.pone.0074551 PMID: 24073214.
44. Samikkannu T, Rao KV, Gandhi N, Saxena SK, Nair MP Human immunodeficiency virus type 1 clade B and C Tat differentially induce indoleamine 2, 3-dioxygenase and serotonin in immature dendritic cells: Implications for neuroAIDS. J Neurovirol 16: 255-263. doi:10.3109/13550284.2010.497809 PMID: 20602605.
45. Gee K, Angel JB, Mishra S, Blahoianu MA, Kumar A (2007) IL-10 regulation by HIV-Tat in primary human monocytic cells: Involvement of calmodulin/calmodulin-dependent protein kinase-activated p38 MAPK and Sp-1 and CREB-1 transcription factors. J Immunol 178: 798-807. PMID: 17202341.
46. Wong JK, Campbell GR, Spector SA (2010) Differential induction of interleukin-10 in monocytes by HIV-1 clade B and clade C Tat proteins. J Biol Chem 285: 18319-18325. doi:10.1074/jbc.M110.120840PMID: 20378550.
47. Gupta S, Boppana R, Mishra GC, Saha B, Mitra D (2008) HIV-1 Tat suppresses gp120-specific T cell response in IL-10-dependent manner. J Immunol 180: 79-88. PMID: 18097007.
48. Chen P, Mayne M, Power C, Nath A (1997) The Tat protein of HIV-1 induces tumor necrosis factoralpha production. Implications for HIV-1-associated neurological diseases. J Biol Chem 272: 22385- 22388. PMID: 9278385.
49. Cohen SS, Li C, Ding L, Cao Y, Pardee AB, et al. (1999) Pronounced acute immunosuppression in vivo mediated by HIV Tat challenge. Proc Natl Acad Sci U S A 96: 10842-10847. PMID: 10485913.
50. Johri MK, Mishra R, Chhatbar C, Unni SK, Singh SK Tits and bits of HIV Tat protein. Expert Opin Biol Ther 11: 269-283. doi:10.1517/14712598.2011.546339 PMID: 21204735.
51. Westendorp MO, Frank R, Ochsenbauer C, Stricker K, Dhein J, et al. (1995) Sensitization of T cells to CD95-mediated apoptosis by HIV-1 Tat and gp120. Nature 375: 497-500. PMID: 7539892.
52. Johri MK, Mishra R, Chhatbar C, Unni SK, Singh SK (2011) Tits and bits of HIV Tat protein. Expert Opin Biol Ther 11: 269-283. doi:10.1517/14712598.2011.546339 PMID: 21204735.
53. Noonan D, Albini A (2000) From the outside in: Extracellular activities of HIV Tat. Adv Pharmacol 48: 229-250. PMID: 10987093.
54. Gupta S, Mitra D (2007) Human immunodeficiency virus-1 Tat protein: Immunological facets of a transcriptional activator. Indian J Biochem Biophys 44: 269-275. PMID: 18341200.
55. Xiao H, Neuveut C, Tiffany HL, Benkirane M, Rich EA, et al. (2000) Selective CXCR4 antagonism by Tat: Implications for in vivo expansion of coreceptor use by HIV-1. Proc Natl Acad Sci U S A 97: 11466-11471. PMID: 11027346.
56. Westendorp MO, Frank R, Ochsenbauer C, Stricker K, Dhein J, et al. (1995) Sensitization of T cells to CD95-mediated apoptosis by HIV-1 Tat and gp120. Nature 375: 497-500. PMID: 7539892.
57. Ensoli B, Buonaguro L, Barillari G, Fiorelli V, Gendelman R, et al. (1993) Release, uptake, and effects of extracellular human immunodeficiency virus type 1 Tat protein on cell growth and viral transactivation. J Virol 67: 277-287. PMID: 8416373.
58. Westendorp MO, Li-Weber M, Frank RW, Krammer PH (1994) Human immunodeficiency virus type 1 Tat upregulates interleukin-2 secretion in activated T cells. J Virol 68: 4177-4185. PMID: 8207793.
59. Rayne F, Debaisieux S, Bonhoure A, Beaumelle B (2010) HIV-1 Tat is unconventionally secreted through the plasma membrane. Cell Biol Int 34: 409-413. doi:10.1042/CBI20090376PMID: 19995346.
60. Bennasser Y, Bahraoui E (2002) HIV-1 Tat protein induces interleukin-10 in human peripheral blood monocytes: Involvement of protein kinase C-betaII and-delta. Faseb J 16: 546-554. PMID: 11919157.
61. Contreras X, Bennasser Y, Bahraoui E (2004) IL-10 production induced by HIV-1 Tat stimulation of human monocytes is dependent on the activation of PKC beta(II) and delta isozymes. Microbes Infect 6: 1182-1190. PMID: 15488737.
62. Contreras X, Bennasser Y, Chazal N, Moreau M, Leclerc C, et al. (2005) Human immunodeficiency virus type 1 Tat protein induces an intracellular calcium increase in human monocytes that requires DHP receptors: Involvement in TNF-alpha production. Virology 332: 316-328. PMID: 15661163.
63. Leghmari K, Bennasser Y, Tkaczuk J, Bahraoui E (2008) HIV-1 Tat protein induces IL-10 production by an alternative TNF-alpha-independent pathway in monocytes: Role of PKC-delta and p38 MAP kinase. Cell Immunol 253: 45-53. doi:10.1016/j.cellimm.2008.04.015 PMID: 18541226.
64. Leghmari K, Bennasser Y, Bahraoui E (2008) HIV-1 Tat protein induces IL-10 production in monocytes by classical and alternative NF-kappaB pathways. Eur J Cell Biol 87: 947-962. doi:10.1016/j.ejcb.2008.06.005 PMID: 18760861.
65. Grela F, Aumeunier A, Bardel E, Van LP, Bourgeois E, et al. (2011) The TLR7 agonist R848 alleviates allergic inflammation by targeting invariant NKT cells to produce IFN-gamma. J Immunol 186: 284- 290. doi:10.4049/jimmunol.1001348 PMID: 21131420.
66. Vives E, Charneau P, van Rietschoten J, Rochat H, Bahraoui E (1994) Effects of the Tat basic domain on human immunodeficiency virus type 1 transactivation, using chemically synthesized Tat protein and Tat peptides. J Virol 68: 3343-3353. PMID: 8151793.
67. Breen EC, Rezai AR, Nakajima K, Beall GN, Mitsuyasu RT, et al. (1990) Infection with HIV is associated with elevated IL-6 levels and production. J Immunol 144: 480-484. PMID: 2295799.
68. Nixon DE, Landay AL Biomarkers of immune dysfunction in HIV. Curr Opin HIV AIDS 5: 498-503. doi:10.1097/COH.0b013e32833ed6f4 PMID: 20978393.
69. Matsumoto T, Miike T, Nelson RP, Trudeau WL, Lockey RF, et al. (1993) Elevated serum levels of IL- 8 in patients with HIV infection. Clin Exp Immunol 93: 149-151. PMID: 8348739.
70. Kedzierska K, Crowe SM (2001) Cytokines and HIV-1: Interactions and clinical implications. Antivir Chem Chemother 12: 133-150. PMID: 12959322.
71. Leghmari K, Contreras X, Moureau C, Bahraoui E (2008) HIV-1 Tat protein induces TNF-alpha and IL-10 production by human macrophages: Differential implication of PKC-betaII and-delta isozymes and MAP kinases ERK1/2 and p38. Cell Immunol 254: 46-55. doi:10.1016/j.cellimm.2008.06.011 PMID: 18692180.
72. Asehnoune K, Strassheim D, Mitra S, Yeol Kim J, Abraham E (2005) Involvement of PKCalpha/beta in TLR4 and TLR2 dependent activation of NF-kappaB. Cell Signal 17: 385-394. PMID: 15567069.
73. Doyle SL, O'Neill LA (2006) Toll-like receptors: from the discovery of NFkappaB to new insights into transcriptional regulations in innate immunity. Biochem Pharmacol 72: 1102-1113. PMID: 16930560.
74. Akira S (2006) TLR signaling. Curr Top Microbiol Immunol 311: 1-16. PMID: 17048703.
75. Wu L, KewalRamani VN (2006) Dendritic-cell interactions with HIV: Infection and viral dissemination. Nat Rev Immunol 6: 859-868. PMID: 17063186.
76. Akhtar LN, Benveniste EN (2011) Viral exploitation of host SOCS protein functions. J Virol 85: 1912- 1921. doi:10.1128/JVI.01857-10 PMID: 21084484.
77. Miller RC, Schlaepfer E, Baenziger S, Crameri R, Zeller S, et al. (2011) HIV interferes with SOCS-1 and -3 expression levels driving immune activation. Eur J Immunol 41: 1058-1069. doi:10.1002/eji.201041198 PMID: 21337543.
78. Yoshimura A, Naka T, Kubo M (2007) SOCS proteins, cytokine signalling and immune regulation. Nat Rev Immunol 7: 454-465. PMID: 17525754.
79. Akhtar LN, Qin H, Muldowney MT, Yanagisawa LL, Kutsch O, et al. (2010) Suppressor of cytokine signaling 3 inhibits antiviral IFN-beta signaling to enhance HIV-1 replication in macrophages. J Immunol 185: 2393-2404. doi:10.4049/jimmunol.0903563 PMID: 20631305.
80. Ryo A, Tsurutani N, Ohba K, Kimura R, Komano J, et al. (2008) SOCS1 is an inducible host factor during HIV-1 infection and regulates the intracellular trafficking and stability of HIV-1 Gag. Proc Natl Acad Sci U S A 105: 294-299. doi:10.1073/pnas.0704831105 PMID: 18172216.
81. Blasdall SA, Geczy AF, Raynes-Greenow CH, Dyer WB, McIntyre LB, et al. (1999) Cytokine profiles in a cohort of long-term survivors of transfusion-acquired HIV-1 infection. J Acquir Immune Defic Syndr Hum Retrovirol 20: 97. PMID: 9928739.
82. Mahajan SD, Agosto-Mojica A, Aalinkeel R, Reynolds JL, Nair BB, et al. Role of chemokine and cytokine polymorphisms in the progression of HIV-1 disease. Biochem Biophys Res Commun 396: 348- 352. doi:10.1016/j.bbrc.2010.04.095 PMID: 20416280.
83. Martinson JA, Montoya CJ, Usuga X, Ronquillo R, Landay AL, et al. Chloroquine modulates HIV-1- induced plasmacytoid dendritic cell alpha interferon: Implication for T-cell activation. Antimicrob Agents Chemother 54: 871-881. doi:10.1128/AAC.01246-09 PMID: 19949061.
84. Contreras X, Bennasser Y, Chazal N, Bahraoui E (2003) [HIV-1 Tat induces TNF-alpha production by human monocytes: Involvement of calcium and PKC pathways]. J Soc Biol 197: 267-275. PMID: 14708348.
85. Mayne M, Bratanich AC, Chen P, Rana F, Nath A, et al. (1998) HIV-1 tat molecular diversity and induction of TNF-alpha: Implications for HIV-induced neurological disease. Neuroimmunomodulation 5: 184-192. PMID: 9730685.
86. Puri RK, Aggarwal BB (1992) Human immunodeficiency virus type 1 tat gene up-regulates interleukin 4 receptors on a human B-lymphoblastoid cell line. Cancer Res 52: 3787-3790. PMID: 1617647.
87. Scala G, Ruocco MR, Ambrosino C, Mallardo M, Giordano V, et al. (1994) The expression of the interleukin 6 gene is induced by the human immunodeficiency virus 1 TAT protein. J Exp Med 179: 961- 971. PMID: 8113688.
88. Kutsch O, Oh J, Nath A, Benveniste EN (2000) Induction of the chemokines interleukin-8 and IP-10 by human immunodeficiency virus type 1 tat in astrocytes. J Virol 74: 9214-9221. PMID: 10982368.
89. Hofman FM, Chen P, Incardona F, Zidovetzki R, Hinton DR (1999) HIV-1 tat protein induces the production of interleukin-8 by human brain-derived endothelial cells. J Neuroimmunol 94: 28-39. PMID: 10376933.
90. Masood R, Lunardi-Iskandar Y, Moudgil T, Zhang Y, Law RE, et al. (1994) IL-10 inhibits HIV-1 replication and is induced by tat. Biochem Biophys Res Commun 202: 374-383. PMID: 8037735.
91. Barreto-de-Souza V, Xavier-Medeiros T, Machado-Motta MC, Bou-Habib DC, Saraiva EM (2008) HIV- 1 infection and HIV-1 Tat protein permit the survival and replication of a non-pathogenic trypanosomatid in macrophages through TGF-beta1 production. Microbes Infect 10: 642-649. doi:10.1016/j.micinf.2008.02.014 PMID: 18457978.
92. Zauli G, Davis BR, Re MC, Visani G, Furlini G, et al. (1992) tat protein stimulates production of transforming growth factor-beta 1 by marrow macrophages: A potential mechanism for human immunodeficiency virus-1-induced hematopoietic suppression. Blood 80: 3036-3043. PMID: 1281686.
93. Poggi A, Zocchi MR (2006) HIV-1 Tat triggers TGF-beta production and NK cell apoptosis that is prevented by pertussis toxin B. Clin Dev Immunol 13: 369-372. PMID: 17162379.
94. Kolson DL, Collman R, Hrin R, Balliet JW, Laughlin M, et al. (1994) Human immunodeficiency virus type 1 Tat activity in human neuronal cells: uptake and trans-activation. J Gen Virol 75 (Pt 8): 1927- 1934. PMID: 8046394.
95. Goldstein G (1996) HIV-1 Tat protein as a potential AIDS vaccine. Nat Med 2: 960-964. PMID: 8782444.
96. Tyagi M, Rusnati M, Presta M, Giacca M (2001) Internalization of HIV-1 tat requires cell surface heparan sulfate proteoglycans. J Biol Chem 276: 3254-3261. PMID: 11024024.
97. Urbinati C, Nicoli S, Giacca M, David G, Fiorentini S, et al. (2009) HIV-1 Tat and heparan sulfate proteoglycan interaction: A novel mechanism of lymphocyte adhesion and migration across the endothelium. Blood 114: 3335-3342. doi:10.1182/blood-2009-01-198945 PMID: 19661268.
98. Li CJ, Ueda Y, Shi B, Borodyansky L, Huang L, et al. (1997) Tat protein induces self-perpetuating permissivity for productive HIV-1 infection. Proc Natl Acad Sci U S A 94: 8116-8120. PMID: 9223324.
99. Gutheil WG, Subramanyam M, Flentke GR, Sanford DG, Munoz E, et al. (1994) Human immunodeficiency virus 1 Tat binds to dipeptidyl aminopeptidase IV (CD26): A possible mechanism for Tat's immunosuppressive activity. Proc Natl Acad Sci U S A 91: 6594-6598. PMID: 7912830.
100. Zocchi MR, Rubartelli A, Morgavi P, Poggi A (1998) HIV-1 Tat inhibits human natural killer cell function by blocking L-type calcium channels. J Immunol 161: 2938-2943. PMID: 9743356.
101. Urbinati C, Mitola S, Tanghetti E, Kumar C, Waltenberger J, et al. (2005) Integrin alphavbeta3 as a target for blocking HIV-1 Tat-induced endothelial cell activation in vitro and angiogenesis in vivo. Arterioscler Thromb Vasc Biol 25: 2315-2320. PMID: 16166568.
102. Zocchi MR, Poggi A, Rubartelli A (1997) The RGD-containing domain of exogenous HIV-1 Tat inhibits the engulfment of apoptotic bodies by dendritic cells. Aids 11: 1227-1235. PMID: 9256940.
103. Sabatier JM, Vives E, Mabrouk K, Benjouad A, Rochat H, et al. (1991) Evidence for neurotoxic activity of tat from human immunodeficiency virus type 1. J Virol 65: 961-967. PMID: 1898974.
104. Albini A, Soldi R, Giunciuglio D, Giraudo E, Benelli R, et al. (1996) The angiogenesis induced by HIV- 1 tat protein is mediated by the Flk-1/KDR receptor on vascular endothelial cells. Nat Med 2: 1371- 1375. PMID: 8946838.
105. Mavilio D, Lombardo G, Kinter A, Fogli M, La-Sala A, et al. (2006) Characterization of the defective interaction between a subset of natural killer cells and dendritic cells in HIV-1 infection. J Exp Med 203: 2339-2350. PMID: 17000867.
106. Sacchi A, Cappelli G, Cairo C, Martino A, Sanarico N, et al. (2007) Differentiation of monocytes into CD1a- dendritic cells correlates with disease progression in HIV-infected patients. J Acquir Immune Defic Syndr 46: 519-528. PMID: 18043312.
107. Benlahrech A, Gotch F, Kelleher P, Patterson S (2011) Loss of NK stimulatory capacity by plasmacytoid and monocyte-derived DC but not myeloid DC in HIV-1 infected patients. PLoS One 6: E17525. doi:10.1371/journal.pone.0017525 PMID: 21408163.
108. Ipp H, Zemlin A (2013) The paradox of the immune response in HIV infection: When inflammation becomes harmful. Clin Chim Acta 416: 96-99. doi:10.1016/j.cca.2012.11.025 PMID: 23228847.
109. Fauci AS (1984) Immunologic abnormalities in the acquired immunodeficiency syndrome (AIDS). Clin Res 32: 491-499. PMID: 6097390.
110. Levine AM (1992) AIDS-associated malignant lymphoma. Med Clin North Am 76: 253-268. PMID: 1727539.
111. Bachelot T, Ray-Coquard I, Menetrier-Caux C, Rastkha M, Duc A, et al. (2003) Prognostic value of serum levels of interleukin 6 and of serum and plasma levels of vascular endothelial growth factor in hormone-refractory metastatic breast cancer patients. Br J Cancer 88: 1721-1726. PMID: 12771987.
112. Beral V, Peterman TA, Berkelman RL, Jaffe HW (1990) Kaposi's sarcoma among persons with AIDS: A sexually transmitted infection? Lancet 335: 123-128. PMID: 1967430.
113. Pantaleo G, Graziosi C, Demarest JF, Butini L, Montroni M, et al. (1993) HIV infection is active and progressive in lymphoid tissue during the clinically latent stage of disease. Nature 362: 355-358. PMID: 8455722.
114. Embretson J, Zupancic M, Ribas JL, Burke A, Racz P, et al. (1993) Massive covert infection of helper T lymphocytes and macrophages by HIV during the incubation period of AIDS. Nature 362: 359-362. PMID: 8096068.
115. Uleri E, Mei A, Mameli G, Poddighe L, Serra C, et al. (2014) HIV Tat acts on endogenous retroviruses of theWfamily and this occurs via Toll-like receptor4: Inference for neuroAIDS. AIDS.