1. AndersenJL, Le RouzicE, PlanellesV (2008) HIV-1 Vpr: mechanisms of G2 arrest and apoptosis. Exp Mol Pathol 85: 2–10.
2. OgawaK, ShibataR, KiyomasuT, HiguchiI, KishidaY, et al. (1989) Mutational analysis of the human immunodeficiency virus vpr open reading frame. J Virol 63: 4110–4114.
3. GummuluruS, EmermanM (1999) Cell cycle- and Vpr-mediated regulation of human immunodeficiency virus type 1 expression in primary and transformed T-cell lines. J Virol 73: 5422–5430.
4. EcksteinDA, ShermanMP, PennML, ChinPS, De NoronhaCM, et al. (2001) HIV-1 Vpr enhances viral burden by facilitating infection of tissue macrophages but not nondividing CD4+ T cells. J Exp Med 194: 1407–1419.
5. HochJ, LangSM, WeegerM, Stahl-HennigC, CoulibalyC, et al. (1995) vpr deletion mutant of simian immunodeficiency virus induces AIDS in rhesus monkeys. J Virol 69: 4807–4813.
6. StevensonM (2003) HIV-1 pathogenesis. Nat Med 9: 853–860.
7. SakaguchiS, MiyaraM, CostantinoCM, HaflerDA (2010) FOXP3+ regulatory T cells in the human immune system. Nat Rev Immunol 10: 490–500.
8. HoriS, NomuraT, SakaguchiS (2003) Control of regulatory T cell development by the transcription factor Foxp3. Science 299: 1057–1061.
9. FissonS, Darrasse-JezeG, LitvinovaE, SeptierF, KlatzmannD, et al. (2003) Continuous activation of autoreactive CD4+CD25+ regulatory T cells in the steady state. J Exp Med 198: 737–746.
10. Vukmanovic-StejicM, ZhangY, CookJE, FletcherJM, McQuaidA, et al. (2006) Human CD4+CD25hiFoxp3+ regulatory T cells are derived by rapid turnover of memory populations in vivo. J Clin Invest 116: 2423–2433.
11. MiyaraM, YoshiokaY, KitohA, ShimaT, WingK, et al. (2009) Functional delineation and differentiation dynamics of human CD4+ T cells expressing the FoxP3 transcription factor. Immunity 30: 899–911.
12. DittmerU, HeH, MesserRJ, SchimmerS, OlbrichAR, et al. (2004) Functional impairment of CD8+ T cells by regulatory T cells during persistent retroviral infection. Immunity 20: 293–303.
13. WeissL, Donkova-PetriniV, CaccavelliL, BalboM, CarbonneilC, et al. (2004) Human immunodeficiency virus-driven expansion of CD4+CD25+ regulatory T cells, which suppress HIV-specific CD4 T-cell responses in HIV-infected patients. Blood 104: 3249–3256.
14. HolmesD, JiangQ, ZhangL, SuL (2008) Foxp3 and Treg cells in HIV-1 infection and immuno-pathogenesis. Immunol Res 41: 248–266.
15. Oswald-RichterK, GrillSM, ShariatN, LeelawongM, SundrudMS, et al. (2004) HIV infection of naturally occurring and genetically reprogrammed human regulatory T-cells. PLoS Biol 2: E198.
16. ApoilPA, PuissantB, RoubinetF, AbbalM, MassipP, et al. (2005) FOXP3 mRNA levels are decreased in peripheral blood CD4+ lymphocytes from HIV-positive patients. J Acquir Immune Defic Syndr 39: 381–385.
17. EggenaMP, BarugahareB, JonesN, OkelloM, MutalyaS, et al. (2005) Depletion of regulatory T cells in HIV infection is associated with immune activation. J Immunol 174: 4407–4414.
18. PereiraLE, VillingerF, OnlamoonN, BryanP, CardonaA, et al. (2007) Simian immunodeficiency virus (SIV) infection influences the level and function of regulatory T cells in SIV-infected rhesus macaques but not SIV-infected sooty mangabeys. J Virol 81: 4445–4456.
19. ChaseAJ, YangHC, ZhangH, BlanksonJN, SilicianoRF (2008) Preservation of FoxP3+ regulatory T cells in the peripheral blood of human immunodeficiency virus type 1-infected elite suppressors correlates with low CD4+ T-cell activation. J Virol 82: 8307–8315.
20. 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.
21. NieC, SatoK, MisawaN, KitayamaH, FujinoH, et al. (2009) Selective infection of CD4+ effector memory T lymphocytes leads to preferential depletion of memory T lymphocytes in R5 HIV-1-infected humanized NOD/SCID/IL-2Rγnull mice. Virology 394: 64–72.
22. SatoK, IzumiT, MisawaN, KobayashiT, YamashitaY, et al. (2010) Remarkable lethal G-to-A mutations in vif-proficient HIV-1 provirus by individual APOBEC3 proteins in humanized mice. J Virol 84: 9546–9556.
23. SatoK, MisawaN, FukuharaM, IwamiS, AnDS, et al. (2012) Vpu augments the initial burst phase of HIV-1 propagation and downregulates BST2 and CD4 in humanized mice. J Virol 86: 5000–5013.
24. SatoK, MisawaN, NieC, SatouY, IwakiriD, et al. (2011) A novel animal model of Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis in humanized mice. Blood 117: 5663–5673.
25. SatoK, NieC, MisawaN, TanakaY, ItoM, et al. (2010) Dynamics of memory and naive CD8+ T lymphocytes in humanized NOD/SCID/IL-2Rγnull mice infected with CCR5-tropic HIV-1. Vaccine 28 Suppl 2: B32–37.
26. BillerbeckE, BarryWT, MuK, DornerM, RiceCM, et al. (2011) Development of human CD4+FoxP3+ regulatory T cells in human stem cell factor-, granulocyte-macrophage colony-stimulating factor-, and interleukin-3-expressing NOD-SCID IL2Rγnull humanized mice. Blood 117: 3076–3086.
27. DuanK, ZhangB, ZhangW, ZhaoY, QuY, et al. (2011) Efficient peripheral construction of functional human regulatory CD4+CD25highFoxp3+ T cells in NOD/SCID mice grafted with fetal human thymus/liver tissues and CD34+ cells. Transpl Immunol 25: 173–179.
28. JiangQ, ZhangL, WangR, JeffreyJ, WashburnML, et al. (2008) FoxP3+CD4+ regulatory T cells play an important role in acute HIV-1 infection in humanized Rag2−/−γC−/− mice in vivo. Blood 112: 2858–2868.
29. OnoeT, KalscheuerH, DanzlN, ChittendenM, ZhaoG, et al. (2011) Human natural regulatory T cell development, suppressive function, and postthymic maturation in a humanized mouse model. J Immunol 187: 3895–3903.
30. KoyanagiY, MilesS, MitsuyasuRT, MerrillJE, VintersHV, et al. (1987) Dual infection of the central nervous system by AIDS viruses with distinct cellular tropisms. Science 236: 819–822.
31. BofillM, MocroftA, LipmanM, MedinaE, BorthwickNJ, et al. (1996) Increased numbers of primed activated CD8+CD38+CD45RO+ T cells predict the decline of CD4+ T cells in HIV-1-infected patients. AIDS 10: 827–834.
32. BenitoJM, LopezM, LozanoS, MartinezP, Gonzalez-LahozJ, et al. (2004) CD38 expression on CD8 T lymphocytes as a marker of residual virus replication in chronically HIV-infected patients receiving antiretroviral therapy. AIDS Res Hum Retroviruses 20: 227–233.
33. KawanoY, TanakaY, MisawaN, TanakaR, KiraJI, et al. (1997) Mutational analysis of human immunodeficiency virus type 1 (HIV-1) accessory genes: requirement of a site in the nef gene for HIV-1 replication in activated CD4+ T cells in vitro and in vivo. J Virol 71: 8456–8466.
34. AdachiA, GendelmanHE, KoenigS, FolksT, WilleyR, et al. (1986) Production of acquired immunodeficiency syndrome-associated retrovirus in human and nonhuman cells transfected with an infectious molecular clone. J Virol 59: 284–291.
35. GohWC, RogelME, KinseyCM, MichaelSF, FultzPN, et al. (1998) HIV-1 Vpr increases viral expression by manipulation of the cell cycle: a mechanism for selection of Vpr in vivo. Nat Med 4: 65–71.
36. VieillardV, StromingerJL, DebreP (2005) NK cytotoxicity against CD4+ T cells during HIV-1 infection: a gp41 peptide induces the expression of an NKp44 ligand. Proc Natl Acad Sci U S A 102: 10981–10986.
37. ChangJJ, AltfeldM (2010) Innate immune activation in primary HIV-1 infection. J Infect Dis 202 Suppl 2: S297–301.
38. WardJ, DavisZ, DeHartJ, ZimmermanE, BosqueA, et al. (2009) HIV-1 Vpr triggers natural killer cell-mediated lysis of infected cells through activation of the ATR-mediated DNA damage response. PLoS Pathog 5: e1000613.
39. RichardJ, SindhuS, PhamTN, BelzileJP, CohenEA (2010) HIV-1 Vpr up-regulates expression of ligands for the activating NKG2D receptor and promotes NK cell-mediated killing. Blood 115: 1354–1363.
40. StevensonM, StanwickTL, DempseyMP, LamonicaCA (1990) HIV-1 replication is controlled at the level of T cell activation and proviral integration. EMBO J 9: 1551–1560.
41. ZackJA, ArrigoSJ, WeitsmanSR, GoAS, HaislipA, et al. (1990) HIV-1 entry into quiescent primary lymphocytes: molecular analysis reveals a labile, latent viral structure. Cell 61: 213–222.
42. Salazar-GonzalezJF, SalazarMG, KeeleBF, LearnGH, GiorgiEE, et al. (2009) Genetic identity, biological phenotype, and evolutionary pathways of transmitted/founder viruses in acute and early HIV-1 infection. J Exp Med 206: 1273–1289.
43. JowettJB, PlanellesV, PoonB, ShahNP, ChenML, et al. (1995) The human immunodeficiency virus type 1 vpr gene arrests infected T cells in the G2+M phase of the cell cycle. J Virol 69: 6304–6313.
44. RogelME, WuLI, EmermanM (1995) The human immunodeficiency virus type 1 vpr gene prevents cell proliferation during chronic infection. J Virol 69: 882–888.
45. ParrishNF, WilenCB, BanksLB, IyerSS, PfaffJM, et al. (2012) Transmitted/founder and chronic subtype C HIV-1 use CD4 and CCR5 receptors with equal efficiency and are not inhibited by blocking the integrin α4β7. PLoS Pathog 8: e1002686.
46. KeeleBF, GiorgiEE, Salazar-GonzalezJF, DeckerJM, PhamKT, et al. (2008) Identification and characterization of transmitted and early founder virus envelopes in primary HIV-1 infection. Proc Natl Acad Sci U S A 105: 7552–7557.
47. KootM, van 't WoutAB, KootstraNA, de GoedeRE, TersmetteM, et al. (1996) Relation between changes in cellular load, evolution of viral phenotype, and the clonal composition of virus populations in the course of human immunodeficiency virus type 1 infection. J Infect Dis 173: 349–354.
48. MosierDE (2009) How HIV changes its tropism: evolution and adaptation? Curr Opin HIV AIDS 4: 125–130.
49. BrenchleyJM, SilvestriG, DouekDC (2010) Nonprogressive and progressive primate immunodeficiency lentivirus infections. Immunity 32: 737–742.
50. BrenchleyJM, SchackerTW, RuffLE, PriceDA, TaylorJH, et al. (2004) CD4+ T cell depletion during all stages of HIV disease occurs predominantly in the gastrointestinal tract. J Exp Med 200: 749–759.
51. VeazeyRS, DeMariaM, ChalifouxLV, ShvetzDE, PauleyDR, et al. (1998) Gastrointestinal tract as a major site of CD4+ T cell depletion and viral replication in SIV infection. Science 280: 427–431.
52. GiavedoniLD, VelasquilloMC, ParodiLM, HubbardGB, HodaraVL (2000) Cytokine expression, natural killer cell activation, and phenotypic changes in lymphoid cells from rhesus macaques during acute infection with pathogenic simian immunodeficiency virus. J Virol 74: 1648–1657.
53. EmilieD, PeuchmaurM, MaillotMC, CrevonMC, BrousseN, et al. (1990) Production of interleukins in human immunodeficiency virus-1-replicating lymph nodes. J Clin Invest 86: 148–159.
54. 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.
55. AkiraS, TakedaK, KaishoT (2001) Toll-like receptors: critical proteins linking innate and acquired immunity. Nat Immunol 2: 675–680.
56. SauterB, AlbertML, FranciscoL, LarssonM, SomersanS, et al. (2000) Consequences of cell death: exposure to necrotic tumor cells, but not primary tissue cells or apoptotic cells, induces the maturation of immunostimulatory dendritic cells. J Exp Med 191: 423–434.
57. BasuS, BinderRJ, SutoR, AndersonKM, SrivastavaPK (2000) Necrotic but not apoptotic cell death releases heat shock proteins, which deliver a partial maturation signal to dendritic cells and activate the NF-κB pathway. Int Immunol 12: 1539–1546.
58. Ostrand-RosenbergS, SinhaP, BeuryDW, ClementsVK (2012) Cross-talk between myeloid-derived suppressor cells (MDSC), macrophages, and dendritic cells enhances tumor-induced immune suppression. Semin Cancer Biol 22: 275–281.
59. GabrilovichDI, NagarajS (2009) Myeloid-derived suppressor cells as regulators of the immune system. Nat Rev Immunol 9: 162–174.
60. GorantlaS, MakarovE, Finke-DwyerJ, GebhartCL, DommW, et al. (2010) CD8+ cell depletion accelerates HIV-1 immunopathology in humanized mice. J Immunol 184: 7082–7091.
61. BaenzigerS, TussiwandR, SchlaepferE, MazzucchelliL, HeikenwalderM, et al. (2006) Disseminated and sustained HIV infection in CD34+ cord blood cell-transplanted Rag2−/−γc−/− mice. Proc Natl Acad Sci U S A 103: 15951–15956.
62. WatanabeS, OhtaS, YajimaM, TerashimaK, ItoM, et al. (2007) Humanized NOD/SCID/IL2Rγnull mice transplanted with hematopoietic stem cells under nonmyeloablative conditions show prolonged life spans and allow detailed analysis of human immunodeficiency virus type 1 pathogenesis. J Virol 81: 13259–13264.
63. WatanabeS, TerashimaK, OhtaS, HoribataS, YajimaM, et al. (2007) Hematopoietic stem cell-engrafted NOD/SCID/IL2Rγnull mice develop human lymphoid systems and induce long-lasting HIV-1 infection with specific humoral immune responses. Blood 109: 212–218.
64. SatoK, KoyanagiY (2011) The mouse is out of the bag: insights and perspectives on HIV-1-infected humanized mouse models. Exp Biol Med (Maywood) 236: 977–985.
65. BergesBK, RowanMR (2011) The utility of the new generation of humanized mice to study HIV-1 infection: transmission, prevention, pathogenesis, and treatment. Retrovirology 8: 65.
66. ShultzLD, BrehmMA, Garcia-MartinezJV, GreinerDL (2012) Humanized mice for immune system investigation: progress, promise and challenges. Nat Rev Immunol 12: 786–798.
67. LevyDN, RefaeliY, MacGregorRR, WeinerDB (1994) Serum Vpr regulates productive infection and latency of human immunodeficiency virus type 1. Proc Natl Acad Sci U S A 91: 10873–10877.
68. HoshinoS, SunB, KonishiM, ShimuraM, SegawaT, et al. (2007) Vpr in plasma of HIV type 1-positive patients is correlated with the HIV type 1 RNA titers. AIDS Res Hum Retroviruses 23: 391–397.
69. ZimmermanES, ShermanMP, BlackettJL, NeidlemanJA, KreisC, et al. (2006) Human immunodeficiency virus type 1 Vpr induces DNA replication stress in vitro and in vivo. J Virol 80: 10407–10418.
70. SakaiK, DimasJ, LenardoMJ (2006) The Vif and Vpr accessory proteins independently cause HIV-1-induced T cell cytopathicity and cell cycle arrest. Proc Natl Acad Sci U S A 103: 3369–3374.
71. WangJ, ShackelfordJM, CasellaCR, ShiversDK, RapaportEL, et al. (2007) The Vif accessory protein alters the cell cycle of human immunodeficiency virus type 1 infected cells. Virology 359: 243–252.
72. IzumiT, IoK, MatsuiM, ShirakawaK, ShinoharaM, et al. (2010) HIV-1 viral infectivity factor interacts with TP53 to induce G2 cell cycle arrest and positively regulate viral replication. Proc Natl Acad Sci U S A 107: 20798–20803.
73. ItoM, HiramatsuH, KobayashiK, SuzueK, KawahataM, et al. (2002) NOD/SCID/γcnull mouse: an excellent recipient mouse model for engraftment of human cells. Blood 100: 3175–3182.
74. AnDS, PoonB, Ho Tsong FangR, WeijerK, BlomB, et al. (2007) Use of a novel chimeric mouse model with a functionally active human immune system to study human immunodeficiency virus type 1 infection. Clin Vaccine Immunol 14: 391–396.