1. SodoraDL, SilvestriG (2008) Immune activation and AIDS pathogenesis. Aids 22: 439–446.
2. ChahroudiA, BosingerSE, VanderfordTH, PaiardiniM, SilvestriG (2012) Natural SIV hosts: showing AIDS the door. Science 335: 1188–1193.
3. LetvinNL, DanielMD, SehgalPK, DesrosiersRC, HuntRD, et al. (1985) Induction of AIDS-like disease in macaque monkeys with T-cell tropic retrovirus STLV-III. Science 230: 71–73.
4. Murphey-CorbM, MartinLN, RanganSR, BaskinGB, GormusBJ, et al. (1986) Isolation of an HTLV-III-related retrovirus from macaques with simian AIDS and its possible origin in asymptomatic mangabeys. Nature 321: 435–437.
5. EstaquierJ, IdziorekT, de BelsF, Barre-SinoussiF, HurtrelB, et al. (1994) Programmed cell death and AIDS: significance of T-cell apoptosis in pathogenic and nonpathogenic primate lentiviral infections. Proc Natl Acad Sci U S A 91: 9431–9435.
6. KornfeldC, PloquinMJ, PandreaI, FayeA, OnangaR, et al. (2005) Antiinflammatory profiles during primary SIV infection in African green monkeys are associated with protection against AIDS. J Clin Invest 115: 1082–1091.
7. BrenchleyJM, PriceDA, SchackerTW, AsherTE, SilvestriG, et al. (2006) Microbial translocation is a cause of systemic immune activation in chronic HIV infection. Nat Med 12: 1365–1371.
8. SilvestriG, SodoraDL, KoupRA, PaiardiniM, O'NeilSP, et al. (2003) Nonpathogenic SIV infection of sooty mangabeys is characterized by limited bystander immunopathology despite chronic high-level viremia. Immunity 18: 441–452.
9. PandreaI, ApetreiC, DufourJ, DillonN, BarbercheckJ, et al. (2006) Simian immunodeficiency virus SIVagm.sab infection of Caribbean African green monkeys: a new model for the study of SIV pathogenesis in natural hosts. J Virol 80: 4858–4867.
10. PandreaIV, GautamR, RibeiroRM, BrenchleyJM, ButlerIF, et al. (2007) Acute loss of intestinal CD4+ T cells is not predictive of simian immunodeficiency virus virulence. J Immunol 179: 3035–3046.
11. FavreD, LedererS, KanwarB, MaZM, ProllS, et al. (2009) Critical loss of the balance between Th17 and T regulatory cell populations in pathogenic SIV infection. PLoS Pathog 5: e1000295.
12. EstesJD, GordonSN, ZengM, ChahroudiAM, DunhamRM, et al. (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: 6798–6807.
13. BosingerSE, LiQ, GordonSN, KlattNR, DuanL, et al. (2009) Global genomic analysis reveals rapid control of a robust innate response in SIV-infected sooty mangabeys. J Clin Invest 119: 3556–3572.
14. JacquelinB, MayauV, TargatB, LiovatAS, KunkelD, et al. (2009) Nonpathogenic SIV infection of African green monkeys induces a strong but rapidly controlled type I IFN response. J Clin Invest 119: 3544–3555.
15. LedererS, FavreD, WaltersKA, ProllS, KanwarB, et al. (2009) Transcriptional profiling in pathogenic and non-pathogenic SIV infections reveals significant distinctions in kinetics and tissue compartmentalization. PLoS Pathog 5: e1000296.
16. Campillo-GimenezL, LaforgeM, FayM, BrusselA, CumontMC, et al. (2010) Non pathogenesis of SIV infection is associated with reduced inflammation and recruitment of plasmacytoid dendritic cells to lymph nodes, not to lack of an interferon type I response, during the acute phase. J Virol 84: 1838–1846.
17. HarrisLD, TabbB, SodoraDL, PaiardiniM, KlattNR, et al. (2010) Downregulation of robust acute type I interferon responses distinguishes nonpathogenic simian immunodeficiency virus (SIV) infection of natural hosts from pathogenic SIV infection of rhesus macaques. J Virol 84: 7886–7891.
18. BosingerSE, SodoraDL, SilvestriG (2011) Generalized immune activation and innate immune responses in simian immunodeficiency virus infection. Curr Opin HIV AIDS 6: 411–418.
19. MirKD, GasperMA, SundaravaradanV, SodoraDL (2011) SIV infection in natural hosts: resolution of immune activation during the acute-to-chronic transition phase. Microbes Infect 13: 14–24.
20. Fitzgerald-BocarslyP, JacobsES (2010) Plasmacytoid dendritic cells in HIV infection: striking a delicate balance. J Leukoc Biol 87: 609–620.
21. FeldmanS, SteinD, AmruteS, DennyT, GarciaZ, et al. (2001) Decreased interferon-alpha production in HIV-infected patients correlates with numerical and functional deficiencies in circulating type 2 dendritic cell precursors. Clin Immunol 101: 201–210.
22. SoumelisV, ScottI, GheyasF, BouhourD, CozonG, et al. (2001) Depletion of circulating natural type 1 interferon-producing cells in HIV-infected AIDS patients. Blood 98: 906–912.
23. BrownKN, TrichelA, Barratt-BoyesSM (2007) Parallel loss of myeloid and plasmacytoid dendritic cells from blood and lymphoid tissue in simian AIDS. J Immunol 178: 6958–6967.
24. MalleretB, ManeglierB, KarlssonI, LebonP, NascimbeniM, et al. (2008) Primary infection with simian immunodeficiency virus: plasmacytoid dendritic cell homing to lymph nodes, type I interferon, and immune suppression. Blood 112: 4598–4608.
25. BrownKN, WijewardanaV, LiuX, Barratt-BoyesSM (2009) Rapid influx and death of plasmacytoid dendritic cells in lymph nodes mediate depletion in acute simian immunodeficiency virus infection. PLoS Pathog 5: e1000413.
26. KwaS, KannanganatS, NigamP, SiddiquiM, ShettyRD, et al. (2011) Plasmacytoid dendritic cells are recruited to the colorectum and contribute to immune activation during pathogenic SIV infection in rhesus macaques. Blood 118: 2763–2773.
27. ReevesRK, EvansTI, GillisJ, WongFE, KangG, et al. (2012) SIV infection induces accumulation of plasmacytoid dendritic cells in the gut mucosa. J Infect Dis 206: 1462–1468.
28. HerbeuvalJP, HardyAW, BoassoA, AndersonSA, DolanMJ, et al. (2005) Regulation of TNF-related apoptosis-inducing ligand on primary CD4+ T cells by HIV-1: role of type I IFN-producing plasmacytoid dendritic cells. Proc Natl Acad Sci U S A 102: 13974–13979.
29. HerbeuvalJP, NilssonJ, BoassoA, HardyAW, KruhlakMJ, et al. (2006) Differential expression of IFN-alpha and TRAIL/DR5 in lymphoid tissue of progressor versus nonprogressor HIV-1-infected patients. Proc Natl Acad Sci U S A 103: 7000–7005.
30. SedaghatAR, GermanJ, TeslovichTM, CofrancescoJJr, JieCC, et al. (2008) Chronic CD4+ T-cell activation and depletion in human immunodeficiency virus type 1 infection: type I interferon-mediated disruption of T-cell dynamics. J Virol 82: 1870–1883.
31. BoassoA, RoyleCM, DoumazosS, AquinoVN, BiasinM, et al. (2011) Overactivation of plasmacytoid dendritic cells inhibits antiviral T-cell responses: a model for HIV immunopathogenesis. Blood 118: 5152–5162.
32. O'BrienM, ManchesO, SabadoRL, Jimenez BarandaS, WangY, et al. (2011) Spatiotemporal trafficking of HIV in human plasmacytoid dendritic cells defines a persistently IFN-alpha-producing and partially matured phenotype. J Clin Invest 121: 1088–1101.
33. BoassoA, ShearerGM (2008) Chronic innate immune activation as a cause of HIV-1 immunopathogenesis. Clin Immunol 126: 235–242.
34. EllegardR, ShankarEM, LarssonM (2011) Targeting HIV-1 innate immune responses therapeutically. Curr Opin HIV AIDS 6: 435–443.
35. RiesM, PritschetK, SchmidtB (2012) Blocking type I interferon production: a new therapeutic option to reduce the HIV-1-induced immune activation. Clin Dev Immunol 2012: 534929.
36. BeignonAS, McKennaK, SkoberneM, ManchesO, DaSilvaI, et al. (2005) Endocytosis of HIV-1 activates plasmacytoid dendritic cells via Toll-like receptor-viral RNA interactions. J Clin Invest 115: 3265–3275.
37. MandlJN, BarryAP, VanderfordTH, KozyrN, ChavanR, et al. (2008) Divergent TLR7 and TLR9 signaling and type I interferon production distinguish pathogenic and nonpathogenic AIDS virus infections. Nat Med 14: 1077–1087.
38. BarratFJ, MeekerT, GregorioJ, ChanJH, UematsuS, et al. (2005) Nucleic acids of mammalian origin can act as endogenous ligands for Toll-like receptors and may promote systemic lupus erythematosus. J Exp Med 202: 1131–1139.
39. BarratFJ, MeekerT, ChanJH, GuiducciC, CoffmanRL (2007) Treatment of lupus-prone mice with a dual inhibitor of TLR7 and TLR9 leads to reduction of autoantibody production and amelioration of disease symptoms. Eur J Immunol 37: 3582–3586.
40. GuiducciC, TripodoC, GongM, SangalettiS, ColomboMP, et al. (2010) Autoimmune skin inflammation is dependent on plasmacytoid dendritic cell activation by nucleic acids via TLR7 and TLR9. J Exp Med 207: 2931–2942.
41. BrownKN, Barratt-BoyesSM (2009) Surface phenotype and rapid quantification of blood dendritic cell subsets in the rhesus macaque. J Med Primatol 38: 272–278.
42. PichlmairA, Reis e SousaC (2007) Innate recognition of viruses. Immunity 27: 370–383.
43. WonderlichER, WijewardanaV, LiuX, Barratt-BoyesSM (2013) Virus-encoded TLR ligands reveal divergent functional responses of mononuclear phagocytes in pathogenic simian immunodeficiency virus infection. J Immunol 190: 2188–2198.
44. HondaK, et al. (2005) IRF-7 is the master regulator of type-1 interferon-dependent immune responses. Nature 434: 772–777.
45. PickerLJ, HagenSI, LumR, Reed-InderbitzinEF, DalyLM, et al. (2004) Insufficient production and tissue delivery of CD4+ memory T cells in rapidly progressive simian immunodeficiency virus infection. J Exp Med 200: 1299–1314.
46. MonceauxV, ViolletL, PetitF, Ho Tsong FangR, CumontMC, et al. (2005) CD8+ T cell dynamics during primary simian immunodeficiency virus infection in macaques: relationship of effector cell differentiation with the extent of viral replication. J Immunol 174: 6898–6908.
47. ShedlockDJ, SilvestriG, WeinerDB (2009) Monkeying around with HIV vaccines: using rhesus macaques to define ‘gatekeepers’ for clinical trials. Nat Rev Immunol 9: 717–728.
48. NascimbeniM, PerieL, ChorroL, DiocouS, KreitmannL, et al. (2009) Plasmacytoid dendritic cells accumulate in spleens from chronically HIV-infected patients but barely participate in interferon-alpha expression. Blood 113: 6112–6119.
49. LonghiMP, TrumpfhellerC, IdoyagaJ, CaskeyM, MatosI, et al. (2009) Dendritic cells require a systemic type I interferon response to mature and induce CD4+ Th1 immunity with poly IC as adjuvant. J Exp Med 206: 1589–1602.
50. SwieckiM, GilfillanS, VermiW, WangY, ColonnaM (2010) Plasmacytoid dendritic cell ablation impacts early interferon responses and antiviral NK and CD8(+) T cell accrual. Immunity 33: 955–966.
51. LevyDE, MarieIJ, DurbinJE (2011) Induction and function of type I and III interferon in response to viral infection. Curr Opin Virol 1: 476–486.
52. VanderfordTH, SlichterC, RogersKA, LawsonBO, ObaedeR, et al. (2012) Treatment of SIV-infected sooty mangabeys with a type-I IFN agonist results in decreased virus replication without inducing hyperimmune activation. Blood 119: 5750–5757.
53. TavelJA, HuangCY, ShenJ, MetcalfJA, DewarR, et al. (2010) Interferon-alpha produces significant decreases in HIV load. J Interferon Cytokine Res 30: 461–464.
54. ManionM, RodriguezB, MedvikK, HardyG, HardingCV, et al. (2012) Interferon-alpha administration enhances CD8+ T cell activation in HIV infection. PLoS One 7: e30306.
55. EstesJD, HarrisLD, KlattNR, TabbB, PittalugaS, et al. (2010) Damaged intestinal epithelial integrity linked to microbial translocation in pathogenic simian immunodeficiency virus infections. PLoS Pathog 6: e1001052.
56. DutertreCA, AmraouiS, DerosaA, JourdainJP, VimeuxL, et al. (2012) Pivotal role of M-DC8+ monocytes from viremic HIV-infected patients in TNFalpha overproduction in response to microbial products. Blood 120: 2259–2268.
57. BiancottoA, GrivelJC, IglehartSJ, VanpouilleC, LiscoA, et al. (2007) Abnormal activation and cytokine spectra in lymph nodes of people chronically infected with HIV-1. Blood 109: 4272–4279.
58. EstesJD, LiQ, ReynoldsMR, WietgrefeS, DuanL, et al. (2006) Premature induction of an immunosuppressive regulatory T cell response during acute simian immunodeficiency virus infection. J Infect Dis 193: 703–712.
59. KatsikisPD, MuellerYM, VillingerF (2011) The cytokine network of acute HIV infection: a promising target for vaccines and therapy to reduce viral set-point? PLoS Pathog 7: e1002055.
60. GearyRS, LeedsJM, HenrySP, MonteithDK, LevinAA (1997) Antisense oligonucleotide inhibitors for the treatment of cancer: 1. Pharmacokinetic properties of phosphorothioate oligodeoxynucleotides. Anticancer Drug Des 12: 383–393.
61. GearyRS, YuRZ, WatanabeT, HenrySP, HardeeGE, et al. (2003) Pharmacokinetics of a tumor necrosis factor-alpha phosphorothioate 2′-O-(2-methoxyethyl) modified antisense oligonucleotide: comparison across species. Drug Metab Dispos 31: 1419–1428.
62. MonteithDK, HornerMJ, GillettNA, ButlerM, GearyR, et al. (1999) Evaluation of the renal effects of an antisense phosphorothioate oligodeoxynucleotide in monkeys. Toxicol Pathol 27: 307–317.
63. MonteithDK, LevinAA (1999) Synthetic oligonucleotides: the development of antisense therapeutics. Toxicol Pathol 27: 8–13.
64. PhillipsJA, CraigSJ, BayleyD, ChristianRA, GearyR, et al. (1997) Pharmacokinetics, metabolism, and elimination of a 20-mer phosphorothioate oligodeoxynucleotide (CGP 69846A) after intravenous and subcutaneous administration. Biochem Pharmacol 54: 657–668.
65. HardyAW, GrahamDR, ShearerGM, HerbeuvalJP (2007) HIV turns plasmacytoid dendritic cells (pDC) into TRAIL-expressing killer pDC and down-regulates HIV coreceptors by Toll-like receptor 7-induced IFN-alpha. Proc Natl Acad Sci U S A 104: 17453–17458.
66. FiorentiniS, RiboldiE, FacchettiF, AvolioM, FabbriM, et al. (2008) HIV-1 matrix protein p17 induces human plasmacytoid dendritic cells to acquire a migratory immature cell phenotype. Proc Natl Acad Sci U S A 105: 3867–3872.
67. OrendiJM, BloemAC, BorleffsJC, WijnholdsFJ, de VosNM, et al. (1998) Activation and cell cycle antigens in CD4+ and CD8+ T cells correlate with plasma human immunodeficiency virus (HIV-1) RNA level in HIV-1 infection. J Infect Dis 178: 1279–1287.
68. SachsenbergN, PerelsonAS, YerlyS, SchockmelGA, LeducD, et al. (1998) Turnover of CD4+ and CD8+ T lymphocytes in HIV-1 infection as measured by Ki-67 antigen. J Exp Med 187: 1295–1303.
69. HacklD, LoschkoJ, SparwasserT, ReindlW, KrugAB (2011) Activation of dendritic cells via TLR7 reduces Foxp3 expression and suppressive function in induced Tregs. Eur J Immunol 41: 1334–1343.
70. PasareC, MedzhitovR (2004) Toll-dependent control mechanisms of CD4 T cell activation. Immunity 21: 733–741.
71. HirotsuC, SrivastavaM (2000) Simultaneous confidence intervals based on one-sided max t test. Stat Prob Letters 49: 25–37.