Simian Immunodeficiency Virus Interactions with Macaque Dendritic Cells

  • Natalia TeleshovaEmail author
  • Nina Derby
  • Elena Martinelli
  • Pavel Pugach
  • Giulia Calenda
  • Melissa Robbiani
Part of the Advances in Experimental Medicine and Biology book series (volume 762)


This chapter summarizes advances in the following areas: (1) dendritic cell (DC)-mediated simian immunodeficiency virus (SIV) transmission, (2) role of DCs in innate and adaptive immunity against SIV, and (3) approaches to harness DC function to induce anti-SIV responses. The nonhuman primate (NHP) model of human immunodeficiency virus (HIV) infection in rhesus macaques and other Asian NHP species is highly relevant to advance the understanding of virus–host interactions critical for transmission and disease pathogenesis. HIV infection is associated with changes in frequency, phenotype, and function of the two principal subsets of DCs, myeloid DCs and plasmacytoid DCs. DC biology during pathogenic SIV infection is strikingly similar to that observed in HIV-infected patients. The NHP models provide an opportunity to dissect the requirements for DC-driven SIV infection and to understand how SIV distorts the DC system to its advantage. Furthermore, the SIV model of mucosal transmission enables the study of the earliest events of infection at the portal of entry that cannot be studied in humans, and, importantly, the involvement of DCs. Nonpathogenic infection in African NHP hosts allows investigations into the role of DCs in disease control. Understanding how DCs are altered during SIV infection is critical to the design of therapeutic and preventative strategies against HIV.


Human Immunodeficiency Virus Dendritic Cell Human Immunodeficiency Virus Infection Simian Immunodeficiency Virus Human Immunodeficiency Virus Replication 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



N.T. is supported by the Swedish Ministry of Foreign Affairs, and the USAID Cooperative Agreement GPO-00-04-00019-00. M.R. is supported by NIH grants R37 AI040877, R01s DE018293, and AI084133, the Swedish Ministry of Foreign Affairs, and the USAID Cooperative Agreement GPO-00-04-00019-00. M.R. is a 2002 Elizabeth Glaser Scientist.


  1. Abel K, Alegria-Hartman MJ, Rothaeusler K, Marthas M, Miller CJ (2002) The relationship between simian immunodeficiency virus RNA levels and the mRNA levels of alpha/beta interferons (IFN-alpha/beta) and IFN-alpha/beta-inducible Mx in lymphoid tissues of rhesus macaques during acute and chronic infection. J Virol 76(16):8433–8445PubMedGoogle Scholar
  2. Abel K, Rocke DM, Chohan B, Fritts L, Miller CJ (2005) Temporal and anatomic relationship between virus replication and cytokine gene expression after vaginal simian immunodeficiency virus infection. J Virol 79(19):12164–12172PubMedGoogle Scholar
  3. Baba TW, Trichel AM, An L, Liska V, Martin LN, Murphey-Corb M, Ruprecht RM (1996) Infection and AIDS in adult macaques after nontraumatic oral exposure to cell-free SIV. Science 272(5267):1486–1489PubMedGoogle Scholar
  4. Barratt-Boyes SM, Wijewardana V (2011) A divergent myeloid dendritic cell response at virus set-point predicts disease outcome in SIV-infected rhesus macaques. J Med Primatol 40(4):206–213PubMedGoogle Scholar
  5. Barratt-Boyes SM, Wijewardana V, Brown KN (2010) In acute pathogenic SIV infection plasmacytoid dendritic cells are depleted from blood and lymph nodes despite mobilization. J Med Primatol 39(4):235–242PubMedGoogle Scholar
  6. Barron MA, Blyveis N, Palmer BE, MaWhinney S, Wilson CC (2003) Influence of plasma viremia on defects in number and immunophenotype of blood dendritic cell subsets in human immunodeficiency virus 1-infected individuals. J Infect Dis 187(1):26–37PubMedGoogle Scholar
  7. Benlahrech A, Harris J, Meiser A, Papagatsias T, Hornig J, Hayes P, Lieber A, Athanasopoulos T, Bachy V, Csomor E, Daniels R, Fisher K, Gotch F, Seymour L, Logan K, Barbagallo R, Klavinskis L, Dickson G, Patterson S (2009) Adenovirus vector vaccination induces expansion of memory CD4 T cells with a mucosal homing phenotype that are readily susceptible to HIV-1. Proc Natl Acad Sci U S A 106(47):19940–19945PubMedGoogle Scholar
  8. Berger G, Durand S, Fargier G, Nguyen XN, Cordeil S, Bouaziz S, Muriaux D, Darlix JL, Cimarelli A (2011) APOBEC3A is a specific inhibitor of the early phases of HIV-1 infection in myeloid cells. PLoS Pathog 7(9):e1002221PubMedGoogle Scholar
  9. Boes M, Cerny J, Massol R, Op Den Brouw M, Kirchhausen T, Chen J, Ploegh HL (2002) T-cell engagement of dendritic cells rapidly rearranges MHC class II transport. Nature 418(6901):983–988PubMedGoogle Scholar
  10. Bosinger SE, Li Q, Gordon SN, Klatt NR, Duan L, Xu L, Francella N, Sidahmed A, Smith AJ, Cramer EM, Zeng M, Masopust D, Carlis JV, Ran L, Vanderford TH, Paiardini M, Isett RB, Baldwin DA, Else JG, Staprans SI, Silvestri G, Haase AT, Kelvin DJ (2009) Global genomic analysis reveals rapid control of a robust innate response in SIV-infected sooty mangabeys. J Clin Invest 119(12):3556–3572PubMedGoogle Scholar
  11. Bosinger SE, Sodora DL, Silvestri G (2011) Generalized immune activation and innate immune responses in simian immunodeficiency virus infection. Curr Opin HIV AIDS 6(5):411–418PubMedGoogle Scholar
  12. Brenchley JM, Price DA, Schacker TW, Asher TE, Silvestri G, Rao S, Kazzaz Z, Bornstein E, Lambotte O, Altmann D, Blazar BR, Rodriguez B, Teixeira-Johnson L, Landay A, Martin JN, Hecht FM, Picker LJ, Lederman MM, Deeks SG, Douek DC (2006) Microbial translocation is a cause of systemic immune activation in chronic HIV infection. Nat Med 12(12):1365–1371PubMedGoogle Scholar
  13. Brenchley JM, Silvestri G, Douek DC (2010) Nonprogressive and progressive primate immunodeficiency lentivirus infections. Immunity 32(6):737–742PubMedGoogle Scholar
  14. Brown KN, Barratt-Boyes SM (2009) Surface phenotype and rapid quantification of blood dendritic cell subsets in the rhesus macaque. J Med Primatol 38(4):272–278PubMedGoogle Scholar
  15. Brown K, Gao W, Alber S, Trichel A, Murphey-Corb M, Watkins SC, Gambotto A, Barratt-Boyes SM (2003) Adenovirus-transduced dendritic cells injected into skin or lymph node prime potent simian immunodeficiency virus-specific T cell immunity in monkeys. J Immunol 171(12):6875–6882PubMedGoogle Scholar
  16. Brown KN, Trichel A, Barratt-Boyes SM (2007) Parallel loss of myeloid and plasmacytoid dendritic cells from blood and lymphoid tissue in simian AIDS. J Immunol 178(11):6958–6967PubMedGoogle Scholar
  17. Brown KN, Wijewardana V, Liu X, Barratt-Boyes SM (2009) Rapid influx and death of plasmacytoid dendritic cells in lymph nodes mediate depletion in acute simian immunodeficiency virus infection. PLoS Pathog 5(5):e1000413PubMedGoogle Scholar
  18. Buchbinder SP, Mehrotra DV, Duerr A, Fitzgerald DW, Mogg R, Li D, Gilbert PB, Lama JR, Marmor M, Del Rio C, McElrath MJ, Casimiro DR, Gottesdiener KM, Chodakewitz JA, Corey L, Robertson MN (2008) Efficacy assessment of a cell-mediated immunity HIV-1 vaccine (the Step Study): a double-blind, randomised, placebo-controlled, test-of-concept trial. Lancet 372(9653):1881–1893PubMedGoogle Scholar
  19. Campillo-Gimenez L, Cumont MC, Fay M, Kared H, Monceaux V, Diop O, Muller-Trutwin M, Hurtrel B, Levy Y, Zaunders J, Dy M, Leite-de-Moraes MC, Elbim C, Estaquier J (2010) AIDS progression is associated with the emergence of IL-17-producing cells early after simian immunodeficiency virus infection. J Immunol 184(2):984–992PubMedGoogle Scholar
  20. Cao W, Bover L, Cho M, Wen X, Hanabuchi S, Bao M, Rosen DB, Wang YH, Shaw JL, Du Q, Li C, Arai N, Yao Z, Lanier LL, Liu YJ (2009) Regulation of TLR7/9 responses in plasmacytoid dendritic cells by BST2 and ILT7 receptor interaction. J Exp Med 206(7):1603–1614PubMedGoogle Scholar
  21. Cavaleiro R, Baptista AP, Soares RS, Tendeiro R, Foxall RB, Gomes P, Victorino RM, Sousa AE (2009) Major depletion of plasmacytoid dendritic cells in HIV-2 infection, an attenuated form of HIV disease. PLoS Pathog 5(11):e1000667PubMedGoogle Scholar
  22. Chow A, Toomre D, Garrett W, Mellman I (2002) Dendritic cell maturation triggers retrograde MHC class II transport from lysosomes to the plasma membrane. Nature 418(6901):988–994PubMedGoogle Scholar
  23. Chung E, Amrute SB, Abel K, Gupta G, Wang Y, Miller CJ, Fitzgerald-Bocarsly P (2005) Characterization of virus-responsive plasmacytoid dendritic cells in the rhesus macaque. Clin Diagn Lab Immunol 12(3):426–435PubMedGoogle Scholar
  24. Co JG, Witwer KW, Gama L, Zink MC, Clements JE (2011) Induction of innate immune responses by SIV in vivo and in vitro: differential expression and function of RIG-I and MDA5. J Infect Dis 204(7):1104–1114PubMedGoogle Scholar
  25. Coates PT, Barratt-Boyes SM, Zhang L, Donnenberg VS, O’Connell PJ, Logar AJ, Duncan FJ, Murphey-Corb M, Donnenberg AD, Morelli AE, Maliszewski CR, Thomson AW (2003) Dendritic cell subsets in blood and lymphoid tissue of rhesus monkeys and their mobilization with Flt3 ligand. Blood 102(7):2513–2521PubMedGoogle Scholar
  26. Crostarosa F, Aravantinou M, Akpogheneta OJ, Jasny E, Shaw A, Kenney J, Piatak M, Lifson JD, Teitelbaum A, Hu L, Chudolij A, Zydowsky TM, Blanchard J, Gettie A, Robbiani M (2009) A macaque model to study vaginal HSV-2/immunodeficiency virus co-infection and the impact of HSV-2 on microbicide efficacy. PLoS One 4(11):e8060PubMedGoogle Scholar
  27. Daniel MD, Kirchhoff F, Czajak SC, Sehgal PK, Desrosiers RC (1992) Protective effects of a live attenuated SIV vaccine with a deletion in the nef gene. Science 258:1938–1941PubMedGoogle Scholar
  28. de Jong MA, de Witte L, Taylor ME, Geijtenbeek TB (2010) Herpes simplex virus type 2 enhances HIV-1 susceptibility by affecting Langerhans cell function. J Immunol 185(3):1633–1641PubMedGoogle Scholar
  29. Desrosiers RC (1990) The simian immunodeficiency viruses. Annu Rev Immunol 8:557–578PubMedGoogle Scholar
  30. Dieu MC, Vanbervliet B, Vicari A, Bridon JM, Oldham E, Ait-Yahia S, Briere F, Zlotnik A, Lebecque S, Caux C (1998) Selective recruitment of immature and mature dendritic cells by distinct chemokines expressed in different anatomic sites. J Exp Med 188(2):373–386PubMedGoogle Scholar
  31. Diop OM, Ploquin MJ, Mortara L, Faye A, Jacquelin B, Kunkel D, Lebon P, Butor C, Hosmalin A, Barre-Sinoussi F, Muller-Trutwin MC (2008) Plasmacytoid dendritic cell dynamics and alpha interferon production during simian immunodeficiency virus infection with a nonpathogenic outcome. J Virol 82(11):5145–5152PubMedGoogle Scholar
  32. Donaghy H, Gazzard B, Gotch F, Patterson S (2003) Dysfunction and infection of freshly isolated blood myeloid and plasmacytoid dendritic cells in patients infected with HIV-1. Blood 101(11):4505–4511PubMedGoogle Scholar
  33. Douek DC, Brenchley JM, Betts MR, Ambrozak DR, Hill BJ, Okamoto Y, Casazza JP, Kuruppu J, Kunstman K, Wolinsky S, Grossman Z, Dybul M, Oxenius A, Price DA, Connors M, Koup RA (2002) HIV preferentially infects HIV-specific CD4+ T cells. Nature 417(6884):95–98PubMedGoogle Scholar
  34. Durudas A, Milush JM, Chen HL, Engram JC, Silvestri G, Sodora DL (2009) Elevated levels of innate immune modulators in lymph nodes and blood are associated with more-rapid disease progression in simian immunodeficiency virus-infected monkeys. J Virol 83(23):12229–12240PubMedGoogle Scholar
  35. Estes JD, Gordon SN, Zeng M, Chahroudi AM, Dunham RM, Staprans SI, Reilly CS, Silvestri G, Haase AT (2008) Early resolution of acute immune activation and induction of PD-1 in SIV-infected sooty mangabeys distinguishes nonpathogenic from pathogenic infection in rhesus macaques. J Immunol 180(10):6798–6807PubMedGoogle Scholar
  36. Flynn BJ, Kastenmuller K, Wille-Reece U, Tomaras GD, Alam M, Lindsay RW, Salazar AM, Perdiguero B, Gomez CE, Wagner R, Esteban M, Park CG, Trumpfheller C, Keler T, Pantaleo G, Steinman RM, Seder R (2011) Immunization with HIV Gag targeted to dendritic cells followed by recombinant New York vaccinia virus induces robust T-cell immunity in nonhuman primates. Proc Natl Acad Sci U S A 108(17):7131–7136PubMedGoogle Scholar
  37. Fontenot D, He H, Hanabuchi S, Nehete PN, Zhang M, Chang M, Nehete B, Wang YH, Ma ZM, Lee HC, Ziegler SF, Courtney AN, Miller CJ, Sun SC, Liu YJ, Sastry KJ (2009) TSLP production by epithelial cells exposed to immunodeficiency virus triggers DC-mediated mucosal infection of CD4+ T cells. Proc Natl Acad Sci U S A 106(39):16776–16781PubMedGoogle Scholar
  38. Frank I, Pope M (2002) The enigma of dendritic cell-immunodeficiency virus interplay. Curr Mol Med 2:229–248PubMedGoogle Scholar
  39. Frank I, Piatak M Jr, Stoessel H, Romani N, Bonnyay D, Lifson JD, Pope M (2002) Infectious and whole inactivated simian immunodeficiency viruses interact similarly with primate dendritic cells (DCs): differential intracellular fate of virions in mature and immature DCs. J Virol 76(6):2936–2951PubMedGoogle Scholar
  40. Frank I, Santos JJ, Mehlhop E, Villamide-Herrera L, Santisteban C, Gettie A, Ignatius R, Lifson JD, Pope M (2003) Presentation of exogenous whole inactivated simian immunodeficiency virus by mature dendritic cells induces CD4+ and CD8+ T-cell responses. J Acquir Immune Defic Syndr 34(1):7–19PubMedGoogle Scholar
  41. Freeman EE, Weiss HA, Glynn JR, Cross PL, Whitworth JA, Hayes RJ (2006) Herpes simplex virus 2 infection increases HIV acquisition in men and women: systematic review and meta-analysis of longitudinal studies. AIDS 20(1):73–83PubMedGoogle Scholar
  42. Gibbs JS, Lackner AA, Lang SM, Simon MA, Sehgal PK, Daniel MD, Desrosiers RC (1995) Progression to AIDS in the absence of a gene for vpr or vpx. J Virol 69(4):2378–2383PubMedGoogle Scholar
  43. Gujer C, Sundling C, Seder RA, Karlsson Hedestam GB, Lore K (2011) Human and rhesus plasmacytoid dendritic cell and B-cell responses to Toll-like receptor stimulation. Immunology 134(3):257–269PubMedGoogle Scholar
  44. Gupta RK, Mlcochova P, Pelchen-Matthews A, Petit SJ, Mattiuzzo G, Pillay D, Takeuchi Y, Marsh M, Towers GJ (2009) Simian immunodeficiency virus envelope glycoprotein counteracts tetherin/BST-2/CD317 by intracellular sequestration. Proc Natl Acad Sci U S A 106(49):20889–20894PubMedGoogle Scholar
  45. Gurney KB, Elliott J, Nassanian H, Song C, Soilleux E, McGowan I, Anton PA, Lee B (2005) Binding and transfer of human immunodeficiency virus by DC-SIGN  +  cells in human rectal mucosa. J Virol 79(9):5762–5773PubMedGoogle Scholar
  46. Hansen SG, Vieville C, Whizin N, Coyne-Johnson L, Siess DC, Drummond DD, Legasse AW, Axthelm MK, Oswald K, Trubey CM, Piatak M Jr, Lifson JD, Nelson JA, Jarvis MA, Picker LJ (2009) Effector memory T cell responses are associated with protection of rhesus monkeys from mucosal simian immunodeficiency virus challenge. Nat Med 15(3):293–299PubMedGoogle Scholar
  47. Heeney JL, Dalgleish AG, Weiss RA (2006) Origins of HIV and the evolution of resistance to AIDS. Science 313(5786):462–466PubMedGoogle Scholar
  48. Hirsch VM, Olmsted RA, Murphey-Corb M, Purcell RH, Johnson PR (1989) An African primate lentivirus (SIVsm) closely related to HIV-2. Nature 339(6223):389–392PubMedGoogle Scholar
  49. Hirsch VM, Sharkey ME, Brown CR, Brichacek B, Goldstein S, Wakefield J, Byrum R, Elkins WR, Hahn BH, Lifson JD, Stevenson M (1998) Vpx is required for dissemination and pathogenesis of SIVsmPBj: evidence of macrophage-dependent viral amplification. Nat Med 4:1401–1408PubMedGoogle Scholar
  50. Hofmann-Lehmann R, Williams AL, Swenerton RK, Li PL, Rasmussen RA, Chenine AL, McClure HM, Ruprecht RM (2002) Quantitation of simian cytokine and beta-chemokine mRNAs, using real-time reverse transcriptase-polymerase chain reaction: variations in expression during chronic primate lentivirus infection. AIDS Res Hum Retroviruses 18(9):627–639PubMedGoogle Scholar
  51. Hrecka K, Hao C, Gierszewska M, Swanson SK, Kesik-Brodacka M, Srivastava S, Florens L, Washburn MP, Skowronski J (2011) Vpx relieves inhibition of HIV-1 infection of macrophages mediated by the SAMHD1 protein. Nature 474(7353):658–661PubMedGoogle Scholar
  52. Hu J, Pope M, O’Doherty U, Brown C, Miller CJ (1998) Immunophenotypic characterization of SIV-infected cells in cervix, vagina and draining lymph nodes of chronically infected rhesus macaques. Lab Invest 78:435–451PubMedGoogle Scholar
  53. Hu J, Miller CJ, O’Doherty U, Marx PA, Pope M (1999) The dendritic cell-T cell milieu of the lymphoid tissue of the tonsil provides a locale in which SIV can reside and propagate at chronic stages of infection. AIDS Res Hum Retroviruses 15:1305–1314PubMedGoogle Scholar
  54. Hu J, Gardner MB, Miller CJ (2000) Simian immunodeficiency virus rapidly penetrates the cervicovaginal mucosa after intravaginal inoculation and infects intraepithelial dendritic cells. J Virol 74:6087–6095PubMedGoogle Scholar
  55. Ignatius R, Isdell F, O’Doherty U, Pope M (1998) Dendritic cells from skin and blood of macaques both promote SIV replication with T cells from different anatomical sites. J Med Primatol 27:121–128PubMedGoogle Scholar
  56. Ignatius R, Steinman RM, Granelli-Piperno A, Messmer D, Stahl-Hennig C, Tenner-Racz K, Racz P, Frank I, Zhong L, Schlesinger-Frankel S, Pope M (2001) Dendritic cells during infection with HIV-1 and SIV. In: Lotze MT, Thomson AW (eds) Dendritic cells, chapter 35, 2nd edn. Academic, London, UK, p 481Google Scholar
  57. Ignatius R, Tenner-Racz K, Messmer D, Gettie A, Blanchard J, Luckay A, Russo C, Smith S, Marx PA, Steinman RM, Racz P, Pope M (2002) Increased macrophage infection upon subcutaneous inoculation of rhesus macaques with simian immunodeficiency virus-loaded dendritic cells or T cells but not with cell-free virus. J Virol 76(19):9787–9797PubMedGoogle Scholar
  58. Jacquelin B, Mayau V, Targat B, Liovat AS, Kunkel D, Petitjean G, Dillies MA, Roques P, Butor C, Silvestri G, Giavedoni LD, Lebon P, Barre-Sinoussi F, Benecke A, Muller-Trutwin MC (2009) Nonpathogenic SIV infection of African green monkeys induces a strong but rapidly controlled type I IFN response. J Clin Invest 119(12):3544–3555PubMedGoogle Scholar
  59. Jameson B, Baribaud F, Pohlmann S, Ghavimi D, Mortari F, Doms RW, Iwasaki A (2002) Expression of DC-SIGN by dendritic cells of intestinal and genital mucosae in humans and rhesus macaques. J Virol 76(4):1866–1875PubMedGoogle Scholar
  60. Jia B, Serra-Moreno R, Neidermyer W, Rahmberg A, Mackey J, Fofana IB, Johnson WE, Westmoreland S, Evans DT (2009) Species-specific activity of SIV Nef and HIV-1 Vpu in overcoming restriction by tetherin/BST2. PLoS Pathog 5(5):e1000429PubMedGoogle Scholar
  61. Kaur A, Di Mascio M, Barabasz A, Rosenzweig M, McClure HM, Perelson AS, Ribeiro RM, Johnson RP (2008) Dynamics of T- and B-lymphocyte turnover in a natural host of simian immunodeficiency virus. J Virol 82(3):1084–1093PubMedGoogle Scholar
  62. Kestler HW 3rd, Ringler DJ, Mori K, Panicali DL, Sehgal PK, Daniel MD, Desrosiers RC (1991) Importance of the nef gene for maintenance of high virus loads and for development of AIDS. Cell 65(4):651–662PubMedGoogle Scholar
  63. Ketloy C, Engering A, Srichairatanakul U, Limsalakpetch A, Yongvanitchit K, Pichyangkul S, Ruxrungtham K (2008) Expression and function of Toll-like receptors on dendritic cells and other antigen presenting cells from non-human primates. Vet Immunol Immunopathol 125(1–2):18–30PubMedGoogle Scholar
  64. Kornfeld C, Ploquin MJ, Pandrea I, Faye A, Onanga R, Apetrei C, Poaty-Mavoungou V, Rouquet P, Estaquier J, Mortara L, Desoutter JF, Butor C, Le Grand R, Roques P, Simon F, Barre-Sinoussi F, Diop OM, Muller-Trutwin MC (2005) Antiinflammatory profiles during primary SIV infection in African green monkeys are associated with protection against AIDS. J Clin Invest 115(4):1082–1091PubMedGoogle Scholar
  65. Kwa S, Kannanganat S, Nigam P, Siddiqui M, Shetty RD, Armstrong W, Ansari A, Bosinger SE, Silvestri G, Amara RR (2011) Plasmacytoid dendritic cells are recruited to the colorectum and contribute to immune activation during pathogenic SIV infection in rhesus macaques. Blood 118(10):2763–2773PubMedGoogle Scholar
  66. Laguette N, Sobhian B, Casartelli N, Ringeard M, Chable-Bessia C, Segeral E, Yatim A, Emiliani S, Schwartz O, Benkirane M (2011) SAMHD1 is the dendritic- and myeloid-cell-specific HIV-1 restriction factor counteracted by Vpx. Nature 474(7353):654–657PubMedGoogle Scholar
  67. Li Q, Estes JD, Schlievert PM, Duan L, Brosnahan AJ, Southern PJ, Reilly CS, Peterson ML, Schultz-Darken N, Brunner KG, Nephew KR, Pambuccian S, Lifson JD, Carlis JV, Haase AT (2009) Glycerol monolaurate prevents mucosal SIV transmission. Nature 458:1034–1038PubMedGoogle Scholar
  68. Lim ES, Emerman M (2011) HIV: going for the watchman. Nature 474(7353):587–588PubMedGoogle Scholar
  69. Lore K (2004) Isolation and immunophenotyping of human and rhesus macaque dendritic cells. Methods Cell Biol 75:623–642PubMedGoogle Scholar
  70. Lore K, Smed-Sorensen A, Vasudevan J, Mascola JR, Koup RA (2005) Myeloid and plasmacytoid dendritic cells transfer HIV-1 preferentially to antigen-specific CD4+ T cells. J Exp Med 201(12):2023–2033PubMedGoogle Scholar
  71. Lu W, Wu X, Lu Y, Guo W, Andrieu JM (2003) Therapeutic dendritic-cell vaccine for simian AIDS. Nat Med 9(1):27–32PubMedGoogle Scholar
  72. Lu W, Arraes LC, Ferreira WT, Andrieu JM (2004) Therapeutic dendritic-cell vaccine for chronic HIV-1 infection. Nat Med 10(12):1359–1365PubMedGoogle Scholar
  73. Malleret B, Karlsson I, Maneglier B, Brochard P, Delache B, Andrieu T, Muller-Trutwin M, Beaumont T, McCune JM, Banchereau J, Le Grand R, Vaslin B (2008a) Effect of SIVmac infection on plasmacytoid and CD1c  +  myeloid dendritic cells in cynomolgus macaques. Immunology 124(2):223–233PubMedGoogle Scholar
  74. Malleret B, Maneglier B, Karlsson I, Lebon P, Nascimbeni M, Perie L, Brochard P, Delache B, Calvo J, Andrieu T, Spreux-Varoquaux O, Hosmalin A, Le Grand R, Vaslin B (2008b) Primary infection with simian immunodeficiency virus: plasmacytoid dendritic cell homing to lymph nodes, type I interferon, and immune suppression. Blood 112(12):4598–4608PubMedGoogle Scholar
  75. Manches O, Bhardwaj N (2009) Resolution of immune activation defines nonpathogenic SIV infection. J Clin Invest 119(12):3512–3515PubMedGoogle Scholar
  76. Mandl JN, Barry AP, Vanderford TH, Kozyr N, Chavan R, Klucking S, Barrat FJ, Coffman RL, Staprans SI, Feinberg MB (2008) Divergent TLR7 and TLR9 signaling and type I interferon production distinguish pathogenic and nonpathogenic AIDS virus infections. Nat Med 14(10):1077–1087PubMedGoogle Scholar
  77. Manel N, Hogstad B, Wang Y, Levy DE, Unutmaz D, Littman DR (2010) A cryptic sensor for HIV-1 activates antiviral innate immunity in dendritic cells. Nature 467(7312):214–217PubMedGoogle Scholar
  78. Mangeat B, Turelli P, Caron G, Friedli M, Perrin L, Trono D (2003) Broad antiretroviral defence by human APOBEC3G through lethal editing of nascent reverse transcripts. Nature 424(6944):99–103PubMedGoogle Scholar
  79. Martinelli E, Tharinger H, Frank I, Arthos J, Piatak M Jr, Lifson JD, Blanchard J, Gettie A, Robbiani M (2011) HSV-2 infection of dendritic cells amplifies a highly susceptible HIV-1 cell target. PLoS Pathog 7(6)Google Scholar
  80. Marx PA, Li Y, Lerche NW, Sutjipto S, Gettie A, Yee JA, Brotman BH, Prince AM, Hanson A, Webster RG et al (1991) Isolation of a simian immunodeficiency virus related to human immunodeficiency virus type 2 from a west African pet sooty mangabey. J Virol 65(8):4480–4485PubMedGoogle Scholar
  81. Mehlhop E, Villamide LA, Frank I, Gettie A, Santisteban C, Messmer D, Ignatius R, Lifson JD, Pope M (2002) Enhanced in vitro stimulation of rhesus macaque dendritic cells for activation of SIV-specific T cell responses. J Immunol Methods 260(1–2):219–234PubMedGoogle Scholar
  82. Melhem NM, Liu XD, Boczkowski D, Gilboa E, Barratt-Boyes SM (2007) Robust CD4+ and CD8+ T cell responses to SIV using mRNA-transfected DC expressing autologous viral Ag. Eur J Immunol 37(8):2164–2173PubMedGoogle Scholar
  83. Messmer D, Ignatius R, Santisteban C, Steinman RM, Pope M (2000) The decreased replicative capacity of simian immunodeficiency virus SIVmac239Delta(nef) is manifest in cultures of immature dendritic cells and T cells. J Virol 74(5):2406–2413PubMedGoogle Scholar
  84. Messmer D, Jacque JM, Santisteban C, Bristow C, Han SY, Villamide-Herrera L, Mehlhop E, Marx PA, Steinman RM, Gettie A, Pope M (2002) Endogenously expressed nef uncouples cytokine and chemokine production from membrane phenotypic maturation in dendritic cells. J Immunol 169(8):4172–4182PubMedGoogle Scholar
  85. Miller CJ, Li Q, Abel K, Kim EY, Ma ZM, Wietgrefe S, La Franco-Scheuch L, Compton L, Duan L, Shore MD, Zupancic M, Busch M, Carlis J, Wolinksy S, Haase AT (2005) Propagation and dissemination of infection after vaginal transmission of simian immunodeficiency virus. J Virol 79(14):9217–9227PubMedGoogle Scholar
  86. Milush JM, Stefano-Cole K, Schmidt K, Durudas A, Pandrea I, Sodora DL (2007) Mucosal innate immune response associated with a timely humoral immune response and slower disease progression after oral transmission of simian immunodeficiency virus to rhesus macaques. J Virol 81(12):6175–6186PubMedGoogle Scholar
  87. Mir KD, Gasper MA, Sundaravaradan V, Sodora DL (2011) SIV infection in natural hosts: resolution of immune activation during the acute-to-chronic transition phase. Microbes Infect 13(1):14–24PubMedGoogle Scholar
  88. Morcock DR, Thomas JA, Gagliardi TD, Gorelick RJ, Roser JD, Chertova EN, Bess JW Jr, Ott DE, Sattentau QJ, Frank I, Pope M, Lifson JD, Henderson LE, Crise BJ (2005) Elimination of retroviral infectivity by N-ethylmaleimide with preservation of functional envelope glycoproteins. J Virol 79(3):1533–1542PubMedGoogle Scholar
  89. Muszil B, Sauermann U, Motzkus D, Stahl-Hennig C, Sopper S (2011) Increased APOBEC3G and APOBEC3F expression is associated with low viral load and prolonged survival in simian immunodeficiency virus infected rhesus monkeys. Retrovirology 8(1):77Google Scholar
  90. Nehete PN, Nehete BP, Manuri P, Hill L, Palmer JL, Sastry KJ (2005) Protection by dendritic cells-based HIV synthetic peptide cocktail vaccine: preclinical studies in the SHIV-rhesus model. Vaccine 23(17–18):2154–2159PubMedGoogle Scholar
  91. Neil SJ, Zang T, Bieniasz PD (2008) Tetherin inhibits retrovirus release and is antagonized by HIV-1 Vpu. Nature 451(7177):425–430PubMedGoogle Scholar
  92. Nigam P, Velu V, Kannanganat S, Chennareddi L, Kwa S, Siddiqui M, Amara RR (2010) Expansion of FOXP3+ CD8 T cells with suppressive potential in colorectal mucosa following a pathogenic simian immunodeficiency virus infection correlates with diminished antiviral T cell response and viral control. J Immunol 184(4):1690–1701PubMedGoogle Scholar
  93. Nigam P, Kwa S, Velu V, Amara RR (2011) Loss of IL-17-producing CD8 T cells during late chronic stage of pathogenic simian immunodeficiency virus infection. J Immunol 186(2):745–753PubMedGoogle Scholar
  94. O’Doherty U, Ignatius R, Bhardwaj N, Pope M (1997) Generation of monocyte-derived cells from the precursors in rhesus macaque blood. J Immunol Methods 207:185–194PubMedGoogle Scholar
  95. Patterson LJ (2011) The “STEP-wise” future of adenovirus-based HIV vaccines. Curr Med Chem 18(26):3981–3986PubMedGoogle Scholar
  96. Patterson S, Rae A, Hockey N, Gilmour J, Gotch F (2001) Plasmacytoid dendritic cells are highly susceptible to human immunodeficiency virus type 1 infection and release infectious virus. J Virol 75(14):6710–6713PubMedGoogle Scholar
  97. Pereira LE, Ansari AA (2009) A case for innate immune effector mechanisms as contributors to disease resistance in SIV-infected sooty mangabeys. Curr HIV Res 7(1):12–22PubMedGoogle Scholar
  98. Peretti S, Shaw A, Blanchard J, Bohm R, Morrow G, Lifson JD, Gettie A, Pope M (2005) Immunomodulatory effects of HSV-2 infection on immature macaque dendritic cells modify innate and adaptive responses. Blood 106:1305–1313PubMedGoogle Scholar
  99. Picker LJ, Hansen SG, Lifson JD (2012) New paradigms for HIV/AIDS vaccine development. Annu Rev Med 63:95–111PubMedGoogle Scholar
  100. Pope M, Elmore D, Ho D, Marx P (1997) Dendritic cell-T cell mixtures, isolated from the skin and mucosae of macaques, support the replication of SIV. AIDS Res Hum Retroviruses 13:819–827PubMedGoogle Scholar
  101. Raffatellu M, Santos RL, Verhoeven DE, George MD, Wilson RP, Winter SE, Godinez I, Sankaran S, Paixao TA, Gordon MA, Kolls JK, Dandekar S, Baumler AJ (2008) Simian immunodeficiency virus-induced mucosal interleukin-17 deficiency promotes Salmonella dissemination from the gut. Nat Med 14(4):421–428PubMedGoogle Scholar
  102. Reeves RK, Fultz PN (2007) Disparate effects of acute and chronic infection with SIVmac239 or SHIV-89.6P on macaque plasmacytoid dendritic cells. Virology 365(2):356–368PubMedGoogle Scholar
  103. Reeves RK, Wei Q, Stallworth J, Fultz PN (2009) Systemic dendritic cell mobilization associated with administration of FLT3 ligand to SIV- and SHIV-infected macaques. AIDS Res Hum Retroviruses 25(12):1313–1328PubMedGoogle Scholar
  104. Ribeiro Dos Santos P, Rancez M, Pretet JL, Michel-Salzat A, Messent V, Bogdanova A, Couedel-Courteille A, Souil E, Cheynier R, Butor C (2011) Rapid dissemination of SIV follows multisite entry after rectal inoculation. PLoS One 6(5):e19493PubMedGoogle Scholar
  105. Rice GI, Bond J, Asipu A, Brunette RL, Manfield IW, Carr IM, Fuller JC, Jackson RM, Lamb T, Briggs TA, Ali M, Gornall H, Couthard LR, Aeby A, Attard-Montalto SP, Bertini E, Bodemer C, Brockmann K, Brueton LA, Corry PC, Desguerre I, Fazzi E, Cazorla AG, Gener B, Hamel BC, Heiberg A, Hunter M, van der Knaap MS, Kumar R, Lagae L, Landrieu PG, Lourenco CM, Marom D, McDermott MF, van der Merwe W, Orcesi S, Prendiville JS, Rasmussen M, Shalev SA, Soler DM, Shinawi M, Spiegel R, Tan TY, Vanderver A, Wakeling EL, Wassmer E, Whittaker E, Lebon P, Stetson DB, Bonthron DT, Crow YJ (2009) Mutations involved in Aicardi-Goutieres syndrome implicate SAMHD1 as regulator of the innate immune response. Nat Genet 41(7):829–832PubMedGoogle Scholar
  106. Sanghavi SK, Reinhart TA (2005) Increased expression of TLR3 in lymph nodes during simian immunodeficiency virus infection: implications for inflammation and immunodeficiency. J Immunol 175(8):5314–5323PubMedGoogle Scholar
  107. Shiver JW, Fu TM, Chen L, Casimiro DR, Davies ME, Evans RK, Zhang ZQ, Simon AJ, Trigona WL, Dubey SA, Huang L, Harris VA, Long RS, Liang X, Handt L, Schleif WA, Zhu L, Freed DC, Persaud NV, Guan L, Punt KS, Tang A, Chen M, Wilson KA, Collins KB, Heidecker GJ, Fernandez VR, Perry HC, Joyce JG, Grimm KM, Cook JC, Keller PM, Kresock DS, Mach H, Troutman RD, Isopi LA, Williams DM, Xu Z, Bohannon KE, Volkin DB, Montefiori DC, Miura A, Krivulka GR, Lifton MA, Kuroda MJ, Schmitz JE, Letvin NL, Caulfield MJ, Bett AJ, Youil R, Kaslow DC, Emini EA (2002) Replication-incompetent adenoviral vaccine vector elicits effective anti-immunodeficiency-virus immunity. Nature 415(6869):331–335PubMedGoogle Scholar
  108. Siddiqui RA, Krawczak M, Platzer M, Sauermann U (2011) Association of TLR7 variants with AIDS-like disease and AIDS vaccine efficacy in rhesus macaques. PLoS One 6(10):e25474PubMedGoogle Scholar
  109. Smed-Sorensen A, Lore K (2011) Dendritic cells at the interface of innate and adaptive immunity to HIV-1. Curr Opin HIV AIDS 6(5):405–410PubMedGoogle Scholar
  110. Soderlund J, Nilsson C, Lore K, Castanos-Velez E, Ekman M, Heiden T, Biberfeld G, Andersson J, Biberfeld P (2004) Dichotomy between CD1a  +  and CD83+ dendritic cells in lymph nodes during SIV infection of macaques. J Med Primatol 33(1):16–24PubMedGoogle Scholar
  111. Soumelis V, Scott I, Gheyas F, Bouhour D, Cozon G, Cotte L, Huang L, Levy JA, Liu YJ (2001) Depletion of circulating natural type 1 interferon-producing cells in HIV-infected AIDS patients. Blood 98(4):906–912PubMedGoogle Scholar
  112. Spira AI, Marx PA, Patterson BK, Mahoney J, Koup RA, Wolinsky SM, Ho DD (1996) Cellular targets of infection and route of viral dissemination after an intravaginal inoculation of simian immunodeficiency virus into rhesus macaques. J Exp Med 183(1):215–225PubMedGoogle Scholar
  113. Stahl-Hennig C, Steinman RM, Tenner-Racz K, Pope M, Stolte N, Matz-Rensing K, Grobschupff G, Raschdorff B, Hunsmann G, Racz P (1999) Rapid infection of oral mucosal-associated lymphoid tissue with simian immunodeficiency virus. Science 285:1261–1265PubMedGoogle Scholar
  114. Stahl-Hennig C, Eisenblatter M, Franz M, Stoiber H, Tenner-Racz K, Suh YS, Jasny E, Falkensammer B, Ugucchioni M, Georgsson G, Baroni C, Dierich MP, Lifson JD, Steinman RM, Uberla K, Racz P, Ignatius R (2007) A single vaccination with attenuated SIVmac 239 via the tonsillar route confers partial protection against challenge with SIVmac 251 at a distant mucosal site, the rectum. Front Biosci 12:2107–2123PubMedGoogle Scholar
  115. Sui Y, Zhu Q, Gagnon S, Dzutsev A, Terabe M, Vaccari M, Venzon D, Klinman D, Strober W, Kelsall B, Franchini G, Belyakov IM, Berzofsky JA (2010) Innate and adaptive immune correlates of vaccine and adjuvant-induced control of mucosal transmission of SIV in macaques. Proc Natl Acad Sci U S A 107(21):9843–9848PubMedGoogle Scholar
  116. Sunseri N, O’Brien M, Bhardwaj N, Landau NR (2011) HIV-1 modified to package SIV Vpx efficiently infects macrophages and dendritic cells. J Virol 85(13):6263–6274PubMedGoogle Scholar
  117. Teleshova N, Jones J, Kenney J, Purcell J, Bohm R, Gettie A, Pope M (2004a) Short term Flt3L treatment effectively mobilizes macaque myeloid dendritic cells. J Leukoc Biol 75:1102–1110PubMedGoogle Scholar
  118. Teleshova N, Kenney J, Jones J, Marshall J, Van Nest G, Dufour J, Bohm R, Lifson JD, Gettie A, Pope M (2004b) CpG-C immunostimulatory oligodeoxyribonucleotide activation of plasmacytoid dendritic cells in rhesus macaques to augment the activation of IFN-gamma-secreting simian immunodeficiency virus-specific T cells. J Immunol 173(3):1647–1657PubMedGoogle Scholar
  119. Tenner-Racz K, Hennig CS, Uberla K, Stoiber H, Ignatius R, Heeney J, Steinman RM, Racz P (2004) Early protection against pathogenic virus infection at a mucosal challenge site after vaccination with attenuated simian immunodeficiency virus. Proc Natl Acad Sci U S A 101(9):3017–3022PubMedGoogle Scholar
  120. Trapp S, Derby NR, Singer R, Shaw A, Williams VG, Turville SG, Bess JW Jr, Lifson JD, Robbiani M (2009) Double-stranded RNA analog poly(I:C) inhibits human immunodeficiency virus amplification in dendritic cells via type I interferon-mediated activation of APOBEC3G. J Virol 83(2):884–895PubMedGoogle Scholar
  121. Turville SG, Arthos J, Cameron PU, Mac Donald K, Clark G, Hart DN, Cunningham AL (2001a) Bitter sweet symphony: defining the role of dendritic cell gp120 receptors in HIV infection. J Clin Virol 22(3):229–239PubMedGoogle Scholar
  122. Turville SG, Arthos J, Mac Donald K, Lynch G, Naif H, Clark G, Hart DN, Cunningham AL (2001b) HIV gp120 receptors on human dendritic cells. Blood 98(8):2482–2488PubMedGoogle Scholar
  123. Turville SG, Santos JJ, Frank I, Cameron PU, Wilkinson J, Miranda-Saksena M, Dable J, Stossel H, Romani N, Piatak M Jr, Lifson JD, Pope M, Cunningham AL (2004) Immunodeficiency virus uptake, turnover, and 2-phase transfer in human dendritic cells. Blood 103(6):2170–2179PubMedGoogle Scholar
  124. Turville SG, Peretti S, Pope M (2006) Lymphocyte-dendritic cell interactions and mucosal acquisition of SIV/HIV infection. Curr Opin HIV AIDS 1(1):3–9PubMedGoogle Scholar
  125. Vagenas P, Aravantinou M, Williams VG, Jasny E, Piatak M Jr, Lifson JD, Salazar AM, Blanchard JL, Gettie A, Robbiani M (2010) A tonsillar PolyICLC/AT-2 SIV therapeutic vaccine maintains low viremia following antiretroviral therapy cessation. PLoS One 5(9):e12891PubMedGoogle Scholar
  126. Van Damme N, Goff D, Katsura C, Jorgenson RL, Mitchell R, Johnson MC, Stephens EB, Guatelli J (2008) The interferon-induced protein BST-2 restricts HIV-1 release and is downregulated from the cell surface by the viral Vpu protein. Cell Host Microbe 3(4):245–252PubMedGoogle Scholar
  127. Veazey RS, DeMaria M, Chalifoux LV, Shvetz DE, Pauley DR, Knight HL, Rosenzweig M, Johnson RP, Desrosiers RC, Lackner AA (1998) Gastrointestinal tract as a major site of CD4+ T cell depletion and viral replication in SIV infection. Science 280:427–431PubMedGoogle Scholar
  128. Velu V, Kannanganat S, Ibegbu C, Chennareddi L, Villinger F, Freeman GJ, Ahmed R, Amara RR (2007) Elevated expression levels of inhibitory receptor programmed death 1 on simian immunodeficiency virus-specific CD8 T cells during chronic infection but not after vaccination. J Virol 81(11):5819–5828PubMedGoogle Scholar
  129. Villamide-Herrera L, Ignatius R, Eller M, Wilkinson K, Griffin C, Mehlhop E, Jones J, Han S-H, Lewis MG, Parrish S, VanCott TC, Lifson JD, Schlesinger S, Mascola JR, Pope M (2004) Macaque dendritic cells infected with SIV-recombinant canarypox ex vivo induce SIV-specific immune responses in vivo. AIDS Res Hum Retroviruses 20:871–884PubMedGoogle Scholar
  130. Wagner GS, Miller CJ, McChesney MB (2002) CD4+ T cells and monocytes elicited by immunization of rhesus monkeys with antigen-pulsed dendritic cells control SIV replication. AIDS Res Hum Retroviruses 18(2):143–148PubMedGoogle Scholar
  131. Wijewardana V, Soloff AC, Liu X, Brown KN, Barratt-Boyes SM (2010) Early myeloid dendritic cell dysregulation is predictive of disease progression in simian immunodeficiency virus infection. PLoS Pathog 6(12):e1001235PubMedGoogle Scholar
  132. Wu L, Bashirova AA, Martin TD, Villamide L, Mehlhop E, Chertov AO, Unutmaz D, Pope M, Carrington M, KewalRamani VN (2002) Rhesus macaque dendritic cells efficiently transmit primate lentiviruses independently of DC-SIGN. Proc Natl Acad Sci U S A 99(3):1568–1573PubMedGoogle Scholar
  133. Xu H, Wang X, Pahar B, Moroney-Rasmussen T, Alvarez X, Lackner AA, Veazey RS (2010) Increased B7-H1 expression on dendritic cells correlates with programmed death 1 expression on T cells in simian immunodeficiency virus-infected macaques and may contribute to T cell dysfunction and disease progression. J Immunol 185(12):7340–7348PubMedGoogle Scholar
  134. Yu Q, Chen D, Konig R, Mariani R, Unutmaz D, Landau NR (2004) APOBEC3B and APOBEC3C are potent inhibitors of simian immunodeficiency virus replication. J Biol Chem 279(51):53379–53386PubMedGoogle Scholar
  135. Zhang ZQ, Wietgrefe SW, Li Q, Shore MD, Duan L, Reilly C, Lifson JD, Haase AT (2004) Roles of substrate availability and infection of resting and activated CD4+ T cells in transmission and acute simian immunodeficiency virus infection. Proc Natl Acad Sci U S A 101(15):5640–5645PubMedGoogle Scholar
  136. Zhang F, Wilson SJ, Landford WC, Virgen B, Gregory D, Johnson MC, Munch J, Kirchhoff F, Bieniasz PD, Hatziioannou T (2009) Nef proteins from simian immunodeficiency viruses are tetherin antagonists. Cell Host Microbe 6(1):54–67PubMedGoogle Scholar
  137. Zimmer ML, Larregina AT, Castillo CM, Capuano S, Jr Falo LD, Murphy-Corb M, Reinhart TA, Barratt-Boyes SM (2002) Disrupted homeostasis of Langerhans cells and interdigitating dendritic cells in monkeys with AIDS. Blood 99(8):2859–2868PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  • Natalia Teleshova
    • 1
    Email author
  • Nina Derby
    • 1
  • Elena Martinelli
    • 1
  • Pavel Pugach
    • 1
  • Giulia Calenda
    • 1
  • Melissa Robbiani
    • 1
  1. 1.HIV and AIDS ProgramCenter for Biomedical Research, Population CouncilNew YorkUSA

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