Retroviruses are genome invaders that have shared a long history of coevolution with vertebrates and their immune system. Found endogenously in genomes as traces of past invasions, retroviruses are also considerable threats to human health when they exist as exogenous viruses such as HIV. The immune response to retroviruses is engaged by germline-encoded sensors of innate immunity that recognize viral components and damage induced by the infection. This response develops with the induction of antiviral effectors and launching of the clonal adaptive immune response, which can contribute to protective immunity. However, retroviruses efficiently evade the immune response, owing to their rapid evolution. The failure of specialized immune cells to respond, a form of neglect, may also contribute to inadequate antiretroviral immune responses. Here, we discuss the mechanisms by which immune responses to retroviruses are mounted at the molecular, cellular, and organismal levels. We also discuss how intrinsic, innate, and adaptive immunity may cooperate or conflict during the generation of immune responses.


Article metrics loading...

Loading full text...

Full text loading...


Literature Cited

  1. Pertel T, Hausmann S, Morger D, Zuger S, Guerra J. 1.  et al. 2011. TRIM5 is an innate immune sensor for the retrovirus capsid lattice. Nature 472:361–65 [Google Scholar]
  2. Portilho DM, Fernandez J, Ringeard M, Machado AK, Boulay A. 2.  et al. 2016. Endogenous TRIM5α function is regulated by SUMOylation and nuclear sequestration for efficient innate sensing in dendritic cells. Cell Rep 14:355–69 [Google Scholar]
  3. Galao RP, Pickering S, Curnock R, Neil SJ. 3.  2014. Retroviral retention activates a Syk-dependent HemITAM in human tetherin. Cell Host Microbe 16:291–303 [Google Scholar]
  4. Monajemi M, Woodworth CF, Benkaroun J, Grant M, Larijani M. 4.  2012. Emerging complexities of APOBEC3G action on immunity and viral fitness during HIV infection and treatment. Retrovirology 9:35 [Google Scholar]
  5. Lahaye X, Manel N. 5.  2015. Viral and cellular mechanisms of the innate immune sensing of HIV. Curr. Opin. Virol. 11:55–62 [Google Scholar]
  6. Silvin A, Manel N. 6.  2015. Innate immune sensing of HIV infection. Curr. Opin. Immunol. 32:54–60 [Google Scholar]
  7. Sporri R, Reis e Sousa C. 7.  2005. Inflammatory mediators are insufficient for full dendritic cell activation and promote expansion of CD4+ T cell populations lacking helper function. Nat. Immunol. 6:163–70 [Google Scholar]
  8. Heil F, Hemmi H, Hochrein H, Ampenberger F, Kirschning C. 8.  et al. 2004. Species-specific recognition of single-stranded RNA via Toll-like receptor 7 and 8. Science 303:1526–29 [Google Scholar]
  9. Kwa S, Kannanganat S, Nigam P, Siddiqui M, Shetty RD. 9.  et al. 2011. Plasmacytoid dendritic cells are recruited to the colorectum and contribute to immune activation during pathogenic SIV infection in rhesus macaques. Blood 118:2763–73 [Google Scholar]
  10. Odendall C, Dixit E, Stavru F, Bierne H, Franz KM. 10.  et al. 2014. Diverse intracellular pathogens activate type III interferon expression from peroxisomes. Nat. Immunol. 15:717–26 [Google Scholar]
  11. Swiecki M, Gilfillan S, Vermi W, Wang Y, Colonna M. 11.  2010. Plasmacytoid dendritic cell ablation impacts early interferon responses and antiviral NK and CD8+ T cell accrual. Immunity 33:955–66 [Google Scholar]
  12. Brewitz A, Eickhoff S, Dahling S, Quast T, Bedoui S. 12.  et al. 2017. CD8+ T cells orchestrate pDC-XCR1+ dendritic cell spatial and functional cooperativity to optimize priming. Immunity 46:205–19 [Google Scholar]
  13. Hardy AW, Graham DR, Shearer GM, Herbeuval JP. 13.  2007. HIV turns plasmacytoid dendritic cells (pDC) into TRAIL-expressing killer pDC and down-regulates HIV coreceptors by Toll-like receptor 7-induced IFN-α. PNAS 104:17453–58 [Google Scholar]
  14. Niess JH, Brand S, Gu X, Landsman L, Jung S. 14.  et al. 2005. CX3CR1-mediated dendritic cell access to the intestinal lumen and bacterial clearance. Science 307:254–58 [Google Scholar]
  15. Silvin A, Yu CI, Lahaye X, Imperatore F. 15.  Brault J-B. et al. 2017. Constitutive resistance to viral infection in human CD141+ dendritic cells. Sci. Immunol. 2:eaai8071 [Google Scholar]
  16. Browne EP. 16.  2013. Toll-like receptor 7 inhibits early acute retroviral infection through rapid lymphocyte responses. J. Virol. 87:7357–66 [Google Scholar]
  17. Kane M, Case LK, Wang C, Yurkovetskiy L, Dikiy S, Golovkina TV. 17.  2011. Innate immune sensing of retroviral infection via Toll-like receptor 7 occurs upon viral entry. Immunity 35:135–45 [Google Scholar]
  18. Geijtenbeek TB, Kwon DS, Torensma R, van Vliet SJ, van Duijnhoven GC. 18.  et al. 2000. DC-SIGN, a dendritic cell-specific HIV-1-binding protein that enhances trans-infection of T cells. Cell 100:587–97 [Google Scholar]
  19. Gringhuis SI, den Dunnen J, Litjens M, van der Vlist M, Geijtenbeek TB. 19.  2009. Carbohydrate-specific signaling through the DC-SIGN signalosome tailors immunity to Mycobacterium tuberculosis, HIV-1 and Helicobacter pylori. . Nat. Immunol. 10:1081–88 [Google Scholar]
  20. Moris A, Nobile C, Buseyne F, Porrot F, Abastado JP, Schwartz O. 20.  2004. DC-SIGN promotes exogenous MHC-I-restricted HIV-1 antigen presentation. Blood 103:2648–54 [Google Scholar]
  21. Hodges A, Sharrocks K, Edelmann M, Baban D, Moris A. 21.  et al. 2007. Activation of the lectin DC-SIGN induces an immature dendritic cell phenotype triggering Rho-GTPase activity required for HIV-1 replication. Nat. Immunol. 8:569–77 [Google Scholar]
  22. Granelli-Piperno A, Golebiowska A, Trumpfheller C, Siegal FP, Steinman RM. 22.  2004. HIV-1-infected monocyte-derived dendritic cells do not undergo maturation but can elicit IL-10 production and T cell regulation. PNAS 101:7669–74 [Google Scholar]
  23. Gringhuis SI, Hertoghs N, Kaptein TM, Zijlstra-Willems EM, Sarrami-Fooroshani R. 23.  et al. 2017. HIV-1 blocks the signaling adaptor MAVS to evade antiviral host defense after sensing of abortive HIV-1 RNA by the host helicase DDX3. Nat. Immunol. 18:225–35 [Google Scholar]
  24. Decalf J, Desdouits M, Rodrigues V, Gobert FX, Gentili M. 24.  et al. 2017. Sensing of HIV-1 entry triggers a type I interferon response in human primary macrophages. J. Virol. 91:e00147–17 [Google Scholar]
  25. Manel N, Hogstad B, Wang Y, Levy DE, Unutmaz D, Littman DR. 25.  2010. A cryptic sensor for HIV-1 activates antiviral innate immunity in dendritic cells. Nature 467:214–17 [Google Scholar]
  26. Rasaiyaah J, Tan CP, Fletcher AJ, Price AJ, Blondeau C. 26.  et al. 2013. HIV-1 evades innate immune recognition through specific cofactor recruitment. Nature 503:402–5 [Google Scholar]
  27. Yan N, Regalado-Magdos AD, Stiggelbout B, Lee-Kirsch MA, Lieberman J. 27.  2010. The cytosolic exonuclease TREX1 inhibits the innate immune response to human immunodeficiency virus type 1. Nat. Immunol. 11:1005–13 [Google Scholar]
  28. Doitsh G, Galloway NL, Geng X, Yang Z, Monroe KM. 28.  et al. 2014. Cell death by pyroptosis drives CD4 T-cell depletion in HIV-1 infection. Nature 505:509–14 [Google Scholar]
  29. Doitsh G, Cavrois M, Lassen KG, Zepeda O, Yang Z. 29.  et al. 2010. Abortive HIV infection mediates CD4 T cell depletion and inflammation in human lymphoid tissue. Cell 143:789–801 [Google Scholar]
  30. Doitsh G, Greene WC. 30.  2016. Dissecting how CD4 T cells are lost during HIV infection. Cell Host Microbe 19:280–91 [Google Scholar]
  31. Munoz-Arias I, Doitsh G, Yang Z, Sowinski S, Ruelas D, Greene WC. 31.  2015. Blood-derived CD4 T cells naturally resist pyroptosis during abortive HIV-1 infection. Cell Host Microbe 18:463–70 [Google Scholar]
  32. Monroe KM, Yang Z, Johnson JR, Geng X, Doitsh G. 32.  et al. 2014. IFI16 DNA sensor is required for death of lymphoid CD4 T cells abortively infected with HIV. Science 343:428–32 [Google Scholar]
  33. Hornung V, Ablasser A, Charrel-Dennis M, Bauernfeind F, Horvath G. 33.  et al. 2009. AIM2 recognizes cytosolic dsDNA and forms a caspase-1-activating inflammasome with ASC. Nature 458:514–18 [Google Scholar]
  34. Thompson MR, Sharma S, Atianand M, Jensen SB, Carpenter S. 34.  et al. 2014. Interferon gamma-inducible protein (IFI) 16 transcriptionally regulates type I interferons and other interferon-stimulated genes and controls the interferon response to both DNA and RNA viruses. J. Biol. Chem. 289:23568–81 [Google Scholar]
  35. Vance RE. 35.  2016. Cytosolic DNA sensing: the field narrows. Immunity 45:227–28 [Google Scholar]
  36. Goldfeld AE, Birch-Limberger K, Schooley RT, Walker BD. 36.  1991. HIV-1 infection does not induce tumor necrosis factor-alpha or interferon-beta gene transcription. J. Acquir. Immune Defic. Syndr. 4:41–47 [Google Scholar]
  37. Vermeire J, Roesch F, Sauter D, Rua R, Hotter D. 37.  et al. 2016. HIV triggers a cGAS-dependent, Vpu- and Vpr-regulated type I interferon response in CD4+ T cells. Cell Rep 17:413–24 [Google Scholar]
  38. Hosmalin A, McIlroy D, Cheynier R, Clauvel JP, Oksenhendler E. 38.  et al. 1995. Splenic interdigitating dendritic cells in humans: characterization and HIV infection frequency in vivo. Adv. Exp. Med. Biol. 378:439–41 [Google Scholar]
  39. Hertoghs N, van der Aar AM, Setiawan LC, Kootstra NA, Gringhuis SI, Geijtenbeek TB. 39.  2015. SAMHD1 degradation enhances active suppression of dendritic cell maturation by HIV-1. J. Immunol. 194:4431–37 [Google Scholar]
  40. Manel N, Littman DR. 40.  2011. Hiding in plain sight: how HIV evades innate immune responses. Cell 147:271–74 [Google Scholar]
  41. Lahaye X, Satoh T, Gentili M, Cerboni S, Conrad C. 41.  et al. 2013. The capsids of HIV-1 and HIV-2 determine immune detection of the viral cDNA by the innate sensor cGAS in dendritic cells. Immunity 39:1132–42 [Google Scholar]
  42. Sunseri N, O'Brien M, Bhardwaj N, Landau NR. 42.  2011. Human immunodeficiency virus type 1 modified to package simian immunodeficiency virus Vpx efficiently infects macrophages and dendritic cells. J. Virol. 85:6263–74 [Google Scholar]
  43. Gao D, Wu J, Wu YT, Du F, Aroh C. 43.  et al. 2013. Cyclic GMP-AMP synthase is an innate immune sensor of HIV and other retroviruses. Science 341:903–6 [Google Scholar]
  44. Bloch N, O'Brien M, Norton TD, Polsky SB, Bhardwaj N, Landau NR. 44.  2014. HIV type 1 infection of plasmacytoid and myeloid dendritic cells is restricted by high levels of SAMHD1 and cannot be counteracted by Vpx. AIDS Res. Hum. Retroviruses 30:195–203 [Google Scholar]
  45. Yoh SM, Schneider M, Seifried J, Soonthornvacharin S, Akleh RE. 45.  et al. 2015. PQBP1 is a proximal sensor of the cGAS-dependent innate response to HIV-1. Cell 161:1293–305 [Google Scholar]
  46. Bobadilla S, Sunseri N, Landau NR. 46.  2013. Efficient transduction of myeloid cells by an HIV-1-derived lentiviral vector that packages the Vpx accessory protein. Gene. Ther. 20:514–20 [Google Scholar]
  47. Puigdomenech I, Casartelli N, Porrot F, Schwartz O. 47.  2013. SAMHD1 restricts HIV-1 cell-to-cell transmission and limits immune detection in monocyte-derived dendritic cells. J. Virol. 87:2846–56 [Google Scholar]
  48. Maelfait J, Bridgeman A, Benlahrech A, Cursi C, Rehwinkel J. 48.  2016. Restriction by SAMHD1 limits cGAS/STING-dependent innate and adaptive immune responses to HIV-1. Cell Rep 16:1492–501 [Google Scholar]
  49. Rowland-Jones SL, Whittle HC. 49.  2007. Out of Africa: what can we learn from HIV-2 about protective immunity to HIV-1?. Nat. Immunol. 8:329–31 [Google Scholar]
  50. de Silva TI, Cotten M, Rowland-Jones SL. 50.  2008. HIV-2: the forgotten AIDS virus. Trends Microbiol 16:588–95 [Google Scholar]
  51. Esbjornsson J, Mansson F, Kvist A, Isberg PE, Nowroozalizadeh S. 51.  et al. 2012. Inhibition of HIV-1 disease progression by contemporaneous HIV-2 infection. N. Engl. J. Med. 367:224–32 [Google Scholar]
  52. Schindler M, Munch J, Kutsch O, Li H, Santiago ML. 52.  et al. 2006. Nef-mediated suppression of T cell activation was lost in a lentiviral lineage that gave rise to HIV-1. Cell 125:1055–67 [Google Scholar]
  53. Arien KK, Abraha A, Quinones-Mateu ME, Kestens L, Vanham G, Arts EJ. 53.  2005. The replicative fitness of primary human immunodeficiency virus type 1 (HIV-1) group M, HIV-1 group O, and HIV-2 isolates. J. Virol. 79:8979–90 [Google Scholar]
  54. Campbell EM, Hope TJ. 54.  2015. HIV-1 capsid: the multifaceted key player in HIV-1 infection. Nat. Rev. Microbiol. 13:471–83 [Google Scholar]
  55. Chin CR, Perreira JM, Savidis G, Portmann JM, Aker AM. 55.  et al. 2015. Direct visualization of HIV-1 replication intermediates shows that capsid and CPSF6 modulate HIV-1 intra-nuclear invasion and integration. Cell Rep 13:1717–31 [Google Scholar]
  56. Peng K, Muranyi W, Glass B, Laketa V, Yant SR. 56.  et al. 2014. Quantitative microscopy of functional HIV post-entry complexes reveals association of replication with the viral capsid. eLife 3:e04114 [Google Scholar]
  57. Li Q, Estes JD, Schlievert PM, Duan L, Brosnahan AJ. 57.  et al. 2009. Glycerol monolaurate prevents mucosal SIV transmission. Nature 458:1034–38 [Google Scholar]
  58. Malleret B, Maneglier B, Karlsson I, Lebon P, Nascimbeni M. 58.  et al. 2008. Primary infection with simian immunodeficiency virus: plasmacytoid dendritic cell homing to lymph nodes, type I interferon, and immune suppression. Blood 112:4598–608 [Google Scholar]
  59. Li Q, Duan L, Estes JD, Ma ZM, Rourke T. 59.  et al. 2005. Peak SIV replication in resting memory CD4+ T cells depletes gut lamina propria CD4+ T cells. Nature 434:1148–52 [Google Scholar]
  60. Lederer S, Favre D, Walters KA, Proll S, Kanwar B. 60.  et al. 2009. Transcriptional profiling in pathogenic and non-pathogenic SIV infections reveals significant distinctions in kinetics and tissue compartmentalization. PLOS Pathog 5:e1000296 [Google Scholar]
  61. Barouch DH, Ghneim K, Bosche WJ, Li Y, Berkemeier B. 61.  et al. 2016. Rapid inflammasome activation following mucosal SIV infection of rhesus monkeys. Cell 165:656–67 [Google Scholar]
  62. Guarda G, Braun M, Staehli F, Tardivel A, Mattmann C. 62.  et al. 2011. Type I interferon inhibits interleukin-1 production and inflammasome activation. Immunity 34:213–23 [Google Scholar]
  63. Reboldi A, Dang EV, McDonald JG, Liang G, Russell DW, Cyster JG. 63.  2014. 25-Hydroxycholesterol suppresses interleukin-1-driven inflammation downstream of type I interferon. Science 345:679–84 [Google Scholar]
  64. Franz KM, Kagan JC. 64.  2017. Innate immune receptors as competitive determinants of cell fate. Mol. Cell 66:750–60 [Google Scholar]
  65. Kane M, Case LK, Kopaskie K, Kozlova A, MacDearmid C. 65.  et al. 2011. Successful transmission of a retrovirus depends on the commensal microbiota. Science 334:245–49 [Google Scholar]
  66. Sewald X, Ladinsky MS, Uchil PD, Beloor J, Pi R. 66.  et al. 2015. Retroviruses use CD169-mediated trans-infection of permissive lymphocytes to establish infection. Science 350:563–67 [Google Scholar]
  67. Menager MM, Littman DR. 67.  2016. Actin dynamics regulates dendritic cell-mediated transfer of HIV-1 to T cells. Cell 164:695–709 [Google Scholar]
  68. Izquierdo-Useros N, Lorizate M, Puertas MC, Rodriguez-Plata MT, Zangger N. 68.  et al. 2012. Siglec-1 is a novel dendritic cell receptor that mediates HIV-1 trans-infection through recognition of viral membrane gangliosides. PLOS Biol 10:e1001448 [Google Scholar]
  69. Rempel H, Calosing C, Sun B, Pulliam L. 69.  2008. Sialoadhesin expressed on IFN-induced monocytes binds HIV-1 and enhances infectivity. PLOS ONE 3:e1967 [Google Scholar]
  70. Nobile C, Petit C, Moris A, Skrabal K, Abastado JP. 70.  et al. 2005. Covert human immunodeficiency virus replication in dendritic cells and in DC-SIGN-expressing cells promotes long-term transmission to lymphocytes. J. Virol. 79:5386–99 [Google Scholar]
  71. Gummuluru S, Rogel M, Stamatatos L, Emerman M. 71.  2003. Binding of human immunodeficiency virus type 1 to immature dendritic cells can occur independently of DC-SIGN and mannose binding C-type lectin receptors via a cholesterol-dependent pathway. J. Virol. 77:12865–74 [Google Scholar]
  72. Boggiano C, Manel N, Littman DR. 72.  2007. Dendritic cell-mediated trans-enhancement of human immunodeficiency virus type 1 infectivity is independent of DC-SIGN. J. Virol. 81:2519–23 [Google Scholar]
  73. Arrighi JF, Pion M, Wiznerowicz M, Geijtenbeek TB, Garcia E. 73.  et al. 2004. Lentivirus-mediated RNA interference of DC-SIGN expression inhibits human immunodeficiency virus transmission from dendritic cells to T cells. J. Virol. 78:10848–55 [Google Scholar]
  74. Burleigh L, Lozach PY, Schiffer C, Staropoli I, Pezo V. 74.  et al. 2006. Infection of dendritic cells (DCs), not DC-SIGN-mediated internalization of human immunodeficiency virus, is required for long-term transfer of virus to T cells. J. Virol. 80:2949–57 [Google Scholar]
  75. Jacquelin B, Mayau V, Targat B, Liovat AS, Kunkel D. 75.  et al. 2009. Nonpathogenic SIV infection of African green monkeys induces a strong but rapidly controlled type I IFN response. J. Clin. Investig. 119:3544–55 [Google Scholar]
  76. Doyle T, Goujon C, Malim MH. 76.  2015. HIV-1 and interferons: Who's interfering with whom?. Nat. Rev. Microbiol. 13:403–13 [Google Scholar]
  77. Eickhoff S, Brewitz A, Gerner MY, Klauschen F, Komander K. 77.  et al. 2015. Robust anti-viral immunity requires multiple distinct T cell-dendritic cell interactions. Cell 162:1322–37 [Google Scholar]
  78. Hor JL, Whitney PG, Zaid A, Brooks AG, Heath WR, Mueller SN. 78.  2015. Spatiotemporally distinct interactions with dendritic cell subsets facilitates CD4+ and CD8+ T cell activation to localized viral infection. Immunity 43:554–65 [Google Scholar]
  79. Greyer M, Whitney PG, Stock AT, Davey GM, Tebartz C. 79.  et al. 2016. T cell help amplifies innate signals in CD8+ DCs for optimal CD8+ T cell priming. Cell Rep 14:586–97 [Google Scholar]
  80. Appay V, Papagno L, Spina CA, Hansasuta P, King A. 80.  et al. 2002. Dynamics of T cell responses in HIV infection. J. Immunol. 168:3660–66 [Google Scholar]
  81. Doisne J-M, Urrutia A, Lacabaratz-Porret C, Goujard C, Meyer L. 81.  et al. 2004. CD8+ T cells specific for EBV, cytomegalovirus, and influenza virus are activated during primary HIV infection. J. Immunol. 173:2410–18 [Google Scholar]
  82. Papagno L, Spina CA, Marchant A, Salio M, Rufer N. 82.  et al. 2004. Immune activation and CD8+ T-cell differentiation towards senescence in HIV-1 infection. PLOS Biol 2:e20 [Google Scholar]
  83. Ndhlovu ZM, Kamya P, Mewalal N, Kloverpris HN, Nkosi T. 83.  et al. 2015. Magnitude and kinetics of CD8+ T cell activation during hyperacute HIV infection impact viral set point. Immunity 43:591–604 [Google Scholar]
  84. Takata H, Buranapraditkun S, Kessing C, Fletcher JL, Muir R. 84.  et al.; for RV254/SEARCH010 RV304/SEARCH013 Study Groups 2017. Delayed differentiation of potent effector CD8+ T cells reducing viremia and reservoir seeding in acute HIV infection. Sci. Transl. Med. 9:eaag1809 [Google Scholar]
  85. Walker B, McMichael A. 85.  2012. The T-cell response to HIV. Cold Spring Harb. Perspect. Med. 2:a007054 [Google Scholar]
  86. Koup RA, Safrit JT, Cao Y, Andrews CA, McLeod G. 86.  et al. 1994. Temporal association of cellular immune responses with the initial control of viremia in primary human immunodeficiency virus type 1 syndrome. J. Virol. 68:4650–55 [Google Scholar]
  87. Okoye A, Park H, Rohankhedkar M, Coyne-Johnson L, Lum R. 87.  et al. 2009. Profound CD4+/CCR5+ T cell expansion is induced by CD8+ lymphocyte depletion but does not account for accelerated SIV pathogenesis. J. Exp. Med. 206:1575–88 [Google Scholar]
  88. Henn MR, Boutwell CL, Charlebois P, Lennon NJ, Power KA. 88.  et al. 2012. Whole genome deep sequencing of HIV-1 reveals the impact of early minor variants upon immune recognition during acute infection. PLOS Pathog 8:e1002529 [Google Scholar]
  89. Bailey JR, Williams TM, Siliciano RF, Blankson JN. 89.  2006. Maintenance of viral suppression in HIV-1–infected HLA-B*57+ elite suppressors despite CTL escape mutations. J. Exp. Med. 203:1357–69 [Google Scholar]
  90. Migueles SA, Weeks KA, Nou E, Berkley AM, Rood JE. 90.  et al. 2009. Defective human immunodeficiency virus-specific CD8+ T-cell polyfunctionality, proliferation, and cytotoxicity are not restored by antiretroviral therapy. J. Virol. 83:11876–89 [Google Scholar]
  91. Oxenius A, Price DA, Easterbrook PJ, O'Callaghan CA, Kelleher AD. 91.  et al. 2000. Early highly active antiretroviral therapy for acute HIV-1 infection preserves immune function of CD8+ and CD4+ T lymphocytes. PNAS 97:73382–87 [Google Scholar]
  92. Frange P, Faye A, Avettand-Fenoel V, Bellaton E, Descamps D. 92.  et al.; for ANRS EPF-CO10 Paediatr. Cohort, ANRS EP47 VISCONTI Study Group 2016. HIV-1 virological remission lasting more than 12 years after interruption of early antiretroviral therapy in a perinatally infected teenager enrolled in the French ANRS EPF-CO10 paediatric cohort: a case report. Lancet HIV 3:e49–54 [Google Scholar]
  93. Saez-Cirion A, Bacchus C, Hocqueloux L, Avettand-Fenoel V, Girault I. 93.  et al.; ANRS VISCONTI Study Group 2013. Post-treatment HIV-1 controllers with a long-term virological remission after the interruption of early initiated antiretroviral therapy ANRS VISCONTI Study. PLOS Pathog 9:e1003211 [Google Scholar]
  94. Whitney JB, Hill AL, Sanisetty S, Penaloza-MacMaster P, Liu J. 94.  et al. 2014. Rapid seeding of the viral reservoir prior to SIV viraemia in rhesus monkeys. Nature 512:74–77 [Google Scholar]
  95. Pauken KE, Sammons MA, Odorizzi PM, Manne S, Godec J. 95.  et al. 2016. Epigenetic stability of exhausted T cells limits durability of reinvigoration by PD-1 blockade. Science 354:1160–65 [Google Scholar]
  96. Champagne P, Ogg GS, King AS, Knabenhans C, Ellefsen K. 96.  et al. 2001. Skewed maturation of memory HIV-specific CD8 T lymphocytes. Nature 410:106–11 [Google Scholar]
  97. Dalod M, Dupuis M, Deschemin J-C, Goujard C, Deveau C. 97.  et al. 1999. Weak anti-HIV CD8+ T-cell effector activity in HIV primary infection. J. Clin. Investig. 104:1431–39 [Google Scholar]
  98. Lecuroux C, Girault I, Cheret A, Versmisse P, Nembot G. 98.  et al.; ANRS 147 OPTIPRIM Clin. Trial 2013. CD8 T-cells from most HIV-infected patients lack ex vivo HIV-suppressive capacity during acute and early infection. PLOS ONE 8:e59767 [Google Scholar]
  99. Paiardini M, Cervasi B, Albrecht H, Muthukumar A, Dunham R. 99.  et al. 2005. Loss of CD127 expression defines an expansion of effector CD8+ T cells in HIV-infected individuals. J. Immunol. 174:2900–9 [Google Scholar]
  100. Trautmann L, Mbitikon-Kobo FM, Goulet JP, Peretz Y, Shi Y. 100.  et al. 2012. Profound metabolic, functional, and cytolytic differences characterize HIV-specific CD8 T cells in primary and chronic HIV infection. Blood 120:3466–77 [Google Scholar]
  101. Saez-Cirion A, Pancino G. 101.  2013. HIV controllers: a genetically determined or inducible phenotype?. Immunol. Rev. 254:281–94 [Google Scholar]
  102. Addo MM, Draenert R, Rathod A, Verrill CL, Davis BT. 102.  et al. 2007. Fully differentiated HIV-1 specific CD8+ T effector cells are more frequently detectable in controlled than in progressive HIV-1 infection. PLOS ONE 2:e321 [Google Scholar]
  103. Saez-Cirion A, Lacabaratz C, Lambotte O, Versmisse P, Urrutia A. 103.  et al.; for ANRS EP36 HIV Controll. Study Group 2007. HIV controllers exhibit potent CD8 T cell capacity to suppress HIV infection ex vivo and peculiar cytotoxic T lymphocyte activation phenotype. PNAS 104:6776–81 [Google Scholar]
  104. Migueles SA, Osborne CM, Royce C, Compton AA, Joshi RP. 104.  et al. 2008. Lytic granule loading of CD8+ T cells is required for HIV-infected cell elimination associated with immune control. Immunity 29:1009–21 [Google Scholar]
  105. Shasha D, Karel D, Angiuli O, Greenblatt A, Ghebremichael M. 105.  et al. 2016. Elite controller CD8+ T cells exhibit comparable viral inhibition capacity, but better sustained effector properties compared to chronic progressors. J. Leukoc. Biol. 100:1425–33 [Google Scholar]
  106. Hersperger AR, Pereyra F, Nason M, Demers K, Sheth P. 106.  et al. 2010. Perforin expression directly ex vivo by HIV-specific CD8 T-cells is a correlate of HIV elite control. PLOS Pathog 6:e1000917 [Google Scholar]
  107. Angin M, Wong G, Papagno L, Versmisse P, David A. 107.  et al.; for ANRS CO5 IMMUNOVIR-2 Study Group 2016. Preservation of lymphopoietic potential and virus suppressive capacity by CD8+ T cells in HIV-2–infected controllers. J. Immunol. 197:2787–95 [Google Scholar]
  108. Thiebaut R, Matheron S, Taieb A, Brun-Vezinet F, Chene G, Autran B. 108. ; for Immunol. Group ANRS CO5 HIV-2 Cohort 2011. Long-term nonprogressors and elite controllers in the ANRS CO5 HIV-2 cohort. AIDS 25:865–67 [Google Scholar]
  109. van der Loeff MFS, Larke N, Kaye S, Berry N, Ariyoshi K. 109.  et al. 2010. Undetectable plasma viral load predicts normal survival in HIV-2-infected people in a West African village. Retrovirology 7:46 [Google Scholar]
  110. van Aalderen MC, Remmerswaal EBM, ten Berge IJM, van Lier RAW. 110.  2014. Blood and beyond: properties of circulating and tissue-resident human virus-specific αβ CD8+ T cells. Eur. J. Immunol. 44:934–44 [Google Scholar]
  111. Hislop AD, Gudgeon NH, Callan MFC, Fazou C, Hasegawa H. 111.  et al. 2001. EBV-specific CD8+ T cell memory: relationships between epitope specificity, cell phenotype, and immediate effector function. J. Immunol. 167:2019–29 [Google Scholar]
  112. Greenough TC, Straubhaar JR, Kamga L, Weiss ER, Brody RM. 112.  et al. 2015. A gene expression signature that correlates with CD8+ T cell expansion in acute EBV infection. J. Immunol. 195:4185–97 [Google Scholar]
  113. Hersperger AR, Martin JN, Shin LY, Sheth PM, Kovacs CM. 113.  et al. 2011. Increased HIV-specific CD8+ T-cell cytotoxic potential in HIV elite controllers is associated with T-bet expression. Blood 117:3799–808 [Google Scholar]
  114. Kaech SM, Tan JT, Wherry EJ, Konieczny BT, Surh CD, Ahmed R. 114.  2003. Selective expression of the interleukin 7 receptor identifies effector CD8 T cells that give rise to long-lived memory cells. Nat. Immunol. 4:1191–98 [Google Scholar]
  115. Kaech SM, Wherry EJ. 115.  2007. Heterogeneity and cell-fate decisions in effector and memory CD8+ T cell differentiation during viral infection. Immunity 27:393–405 [Google Scholar]
  116. Intlekofer AM, Takemoto N, Wherry EJ, Longworth SA, Northrup JT. 116.  et al. 2005. Effector and memory CD8+ T cell fate coupled by T-bet and eomesodermin. Nat. Immunol. 6:1236–44 [Google Scholar]
  117. Chang JT, Palanivel VR, Kinjyo I, Schambach F, Intlekofer AM. 117.  et al. 2007. Asymmetric T lymphocyte division in the initiation of adaptive immune responses. Science 315:1687–91 [Google Scholar]
  118. Gerlach C, Heijst JWJV, Swart E, Sie D, Armstrong N. 118.  et al. 2010. One naive T cell, multiple fates in CD8+ T cell differentiation. J. Exp. Med. 207:1235–46 [Google Scholar]
  119. Beuneu H, Lemaître F, Deguine J, Moreau HD, Bouvier I. 119.  et al. 2010. Visualizing the functional diversification of CD8+ T cell responses in lymph nodes. Immunity 33:412–23 [Google Scholar]
  120. Hu JK, Kagari T, Clingan JM, Matloubian M. 120.  2011. Expression of chemokine receptor CXCR3 on T cells affects the balance between effector and memory CD8 T-cell generation. PNAS 108:E118–27 [Google Scholar]
  121. King CG, Koehli S, Hausmann B, Schmaler M, Zehn D, Palmer E. 121.  2012. T cell affinity regulates asymmetric division, effector cell differentiation, and tissue pathology. Immunity 37:709–20 [Google Scholar]
  122. Bachmann MF, Speiser DE, Ohashi PS. 122.  1997. Functional maturation of an antiviral cytotoxic T-cell response. J. Virol. 71:5764–68 [Google Scholar]
  123. Busch DH, Pamer EG. 123.  1999. T cell affinity maturation by selective expansion during infection. J. Exp. Med. 189:701–10 [Google Scholar]
  124. Zehn D, Lee SY, Bevan MJ. 124.  2009. Complete but curtailed T-cell response to very low-affinity antigen. Nature 458:211–14 [Google Scholar]
  125. Lichterfeld M, Yu XG, Mui SK, Williams KL, Trocha A. 125.  et al. 2007. Selective depletion of high-avidity human immunodeficiency virus type 1 (HIV-1)-specific CD8+ T cells after early HIV-1 infection. J. Virol. 81:4199–214 [Google Scholar]
  126. Almeida JR, Price DA, Papagno L, Arkoub ZA, Sauce D. 126.  et al. 2007. Superior control of HIV-1 replication by CD8+ T cells is reflected by their avidity, polyfunctionality, and clonal turnover. J. Exp. Med. 204:2473–85 [Google Scholar]
  127. Lecuroux C, Saez-Cirion A, Girault I, Versmisse P, Boufassa F. 127.  et al. 2014. Both HLA-B*57 and plasma HIV RNA levels contribute to the HIV-specific CD8+ T cell response in HIV controllers. J. Virol. 88:176–87 [Google Scholar]
  128. Ozga AJ, Moalli F, Abe J, Swoger J, Sharpe J. 128.  et al. 2016. pMHC affinity controls duration of CD8+ T cell-DC interactions and imprints timing of effector differentiation versus expansion. J. Exp. Med. 213:2811–29 [Google Scholar]
  129. Joshi NS, Cui W, Chandele A, Lee HK, Urso DR. 129.  et al. 2007. Inflammation directs memory precursor and short-lived effector CD8+ T cell fates via the graded expression of T-bet transcription factor. Immunity 27:281–95 [Google Scholar]
  130. Kurachi M, Kurachi J, Suenaga F, Tsukui T, Abe J. 130.  et al. 2011. Chemokine receptor CXCR3 facilitates CD8+ T cell differentiation into short-lived effector cells leading to memory degeneration. J. Exp. Med. 208:1605–20 [Google Scholar]
  131. Jacquelin B, Mayau V, Targat B, Liovat A-S, Kunkel D. 131.  et al. 2009. Nonpathogenic SIV infection of African green monkeys induces a strong but rapidly controlled type I IFN response. J. Clin. Investig. 119:3544–55 [Google Scholar]
  132. Malleret B, Manéglier B, Karlsson I, Lebon P, Nascimbeni M. 132.  et al. 2008. Primary infection with simian immunodeficiency virus: plasmacytoid dendritic cell homing to lymph nodes, type I interferon, and immune suppression. Blood 112:4598–608 [Google Scholar]
  133. Mattapallil JJ, Douek DC, Hill B, Nishimura Y, Martin M, Roederer M. 133.  2005. Massive infection and loss of memory CD4+ T cells in multiple tissues during acute SIV infection. Nature 434:1093–97 [Google Scholar]
  134. Stacey AR, Norris PJ, Qin L, Haygreen EA, Taylor E. 134.  et al. 2009. Induction of a striking systemic cytokine cascade prior to peak viremia in acute human immunodeficiency virus type 1 infection, in contrast to more modest and delayed responses in acute hepatitis B and C virus infections. J. Virol. 83:3719–33 [Google Scholar]
  135. Zou W, Lackner AA, Simon M, Durand-Gasselin I, Galanaud P. 135.  et al. 1997. Early cytokine and chemokine gene expression in lymph nodes of macaques infected with simian immunodeficiency virus is predictive of disease outcome and vaccine efficacy. J. Virol. 71:1227–36 [Google Scholar]
  136. Estes JD, Li Q, Reynolds MR, Wietgrefe S, Duan L. 136.  et al. 2006. Premature induction of an immunosuppressive regulatory T cell response during acute simian immunodeficiency virus infection. J. Infect. Dis. 193:703–12 [Google Scholar]
  137. Douek DC, Brenchley JM, Betts MR, Ambrozak DR, Hill BJ. 137.  et al. 2002. HIV preferentially infects HIV-specific CD4+ T cells. Nature 417:95–98 [Google Scholar]
  138. Huang J, Burke PS, Cung TDH, Pereyra F, Toth I. 138.  et al. 2010. Leukocyte immunoglobulin-like receptors maintain unique antigen-presenting properties of circulating myeloid dendritic cells in HIV-1-infected elite controllers. J. Virol. 84:9463–71 [Google Scholar]
  139. Chen H, Li C, Huang J, Cung T, Seiss K. 139.  et al. 2011. CD4+ T cells from elite controllers resist HIV-1 infection by selective upregulation of p21. J. Clin. Investig. 121:1549–60 [Google Scholar]
  140. Saez-Cirion A, Hamimi C, Bergamaschi A, David A, Versmisse P. 140.  et al. 2011. Restriction of HIV-1 replication in macrophages and CD4+ T cells from HIV controllers. Blood 118:955–64 [Google Scholar]
  141. Hamimi C, David A, Versmisse P, Weiss L, Bruel T. 141.  et al.; ANRS CO21 CODEX cohort 2016. Dendritic cells from HIV controllers have low susceptibility to HIV-1 infection in vitro but high capacity to capture HIV-1 particles. PLOS ONE 11:e0160251 [Google Scholar]
  142. Martin-Gayo E, Buzon MJ, Ouyang Z, Hickman T, Cronin J. 142.  et al. 2015. Potent cell-intrinsic immune responses in dendritic cells facilitate HIV-1-specific T cell immunity in HIV-1 elite controllers. PLOS Pathog 11:e1004930 [Google Scholar]
  143. Vingert B, Benati D, Lambotte O, de Truchis P, Slama L. 143.  et al. 2012. HIV controllers maintain a population of highly efficient Th1 effector cells in contrast to patients treated in the long term. J. Virol. 86:10661–74 [Google Scholar]
  144. Rosenberg ES, Billingsley JM, Caliendo AM, Boswell SL, Sax PE. 144.  et al. 1997. Vigorous HIV-1-specific CD4+ T cell responses associated with control of viremia. Science 278:1447–50 [Google Scholar]
  145. Soghoian DZ, Jessen H, Flanders M, Sierra-Davidson K, Cutler S. 145.  et al. 2012. HIV-specific cytolytic CD4 T cell responses during acute HIV infection predict disease outcome. Sci. Transl. Med. 4:123ra25 [Google Scholar]
  146. Chevalier MF, Jülg B, Pyo A, Flanders M, Ranasinghe S. 146.  et al. 2011. HIV-1-specific interleukin-21+ CD4+ T cell responses contribute to durable viral control through the modulation of HIV-specific CD8+ T cell function. J. Virol. 85:733–41 [Google Scholar]
  147. Kalams SA, Buchbinder SP, Rosenberg ES, Billingsley JM, Colbert DS. 147.  et al. 1999. Association between virus-specific cytotoxic T-lymphocyte and helper responses in human immunodeficiency virus type 1 infection. J. Virol. 73:6715–20 [Google Scholar]
  148. Okoye AA, Picker LJ. 148.  2013. CD4+ T-cell depletion in HIV infection: mechanisms of immunological failure. Immunol. Rev. 254:54–64 [Google Scholar]
  149. Benati D, Galperin M, Lambotte O, Gras S, Lim A. 149.  et al. 2016. Public T cell receptors confer high-avidity CD4 responses to HIV controllers. J. Clin. Investig. 126:2093–108 [Google Scholar]
  150. Duvall MG, Precopio ML, Ambrozak DA, Jaye A, McMichael AJ. 150.  et al. 2008. Polyfunctional T cell responses are a hallmark of HIV-2 infection. Eur J. Immunol. 38:350–63 [Google Scholar]
  151. Potter SJ, Lacabaratz C, Lambotte O, Perez-Patrigeon S, Vingert B. 151.  et al. 2007. Preserved central memory and activated effector memory CD4+ T-cell subsets in human immunodeficiency virus controllers: an ANRS EP36 study. J. Virol. 81:13904–15 [Google Scholar]
  152. Melamed A, Laydon DJ, Al Khatib H, Rowan AG, Taylor GP, Bangham CR. 152.  2015. HTLV-1 drives vigorous clonal expansion of infected CD8+ T cells in natural infection. Retrovirology 12:91 [Google Scholar]
  153. Greten TF, Slansky JE, Kubota R, Soldan SS, Jaffee EM. 153.  et al. 1998. Direct visualization of antigen-specific T cells: HTLV-1 Tax11–19- specific CD8+ T cells are activated in peripheral blood and accumulate in cerebrospinal fluid from HAM/TSP patients. PNAS 95:7568–73 [Google Scholar]
  154. Rowan AG, Witkover A, Melamed A, Tanaka Y, Cook LB. 154.  et al. 2016. T cell receptor Vβ staining identifies the malignant clone in adult T cell leukemia and reveals killing of leukemia cells by autologous CD8+ T cells. PLOS Pathog 12:e1006030 [Google Scholar]
  155. Hasenkrug KJ, Dittmer U. 155.  2000. The role of CD4 and CD8 T cells in recovery and protection from retroviral infection: lessons from the Friend virus model. Virology 272:244–49 [Google Scholar]
  156. Hasenkrug KJ, Chesebro B. 156.  1997. Immunity to retroviral infection: the Friend virus model. PNAS 94:7811–16 [Google Scholar]
  157. Santiago ML, Montano M, Benitez R, Messer RJ, Yonemoto W. 157.  et al. 2008. Apobec3 encodes Rfv3, a gene influencing neutralizing antibody control of retrovirus infection. Science 321:1343–46 [Google Scholar]
  158. Tomaras GD, Haynes BF. 158.  2009. HIV-1-specific antibody responses during acute and chronic HIV-1 infection. Curr. Opin. HIV AIDS 4:373–79 [Google Scholar]
  159. Victora GD, Mouquet H. 159.  2017. What are the primary limitations in B-cell affinity maturation, and how much affinity maturation can we drive with vaccination? Lessons from the antibody response to HIV-1. Cold Spring Harb. Perspect. Biol.In press [Google Scholar]
  160. Mouquet H. 160.  2014. Antibody B cell responses in HIV-1 infection. Trends Immunol 35:549–61 [Google Scholar]
  161. Rusert P, Kouyos RD, Kadelka C, Ebner H, Schanz M. 161.  et al.; Swiss HIV Cohort Study 2016. Determinants of HIV-1 broadly neutralizing antibody induction. Nat. Med. 22:1260–67 [Google Scholar]
  162. Klein F, Diskin R, Scheid JF, Gaebler C, Mouquet H. 162.  et al. 2013. Somatic mutations of the immunoglobulin framework are generally required for broad and potent HIV-1 neutralization. Cell 153:126–38 [Google Scholar]
  163. Kelsoe G, Haynes BF. 163.  2017. What are the primary limitations in B-cell affinity maturation, and how much affinity maturation can we drive with vaccination? Breaking through immunity's glass ceiling. Cold Spring Harb. Perspect. Biol. In press [Google Scholar]
  164. Moir S, Fauci AS. 164.  2013. Insights into B cells and HIV‐specific B‐cell responses in HIV‐infected individuals. Immunol. Rev. 254:207–24 [Google Scholar]
  165. Keele BF, Tazi L, Gartner S, Liu Y, Burgon TB. 165.  et al. 2008. Characterization of the follicular dendritic cell reservoir of human immunodeficiency virus type 1. J. Virol. 82:5548–61 [Google Scholar]
  166. Perreau M, Savoye A-L, Crignis ED, Corpataux J-M, Cubas R. 166.  et al. 2013. Follicular helper T cells serve as the major CD4 T cell compartment for HIV-1 infection, replication, and production. J. Exp. Med. 210:143–56 [Google Scholar]
  167. Boritz EA, Darko S, Swaszek L, Wolf G, Wells D. 167.  et al. 2016. Multiple origins of virus persistence during natural control of HIV infection. Cell 166:1004–15 [Google Scholar]
  168. Ackerman ME, Mikhailova A, Brown EP, Dowell KG, Walker BD. 168.  et al. 2016. Polyfunctional HIV-specific antibody responses are associated with spontaneous HIV control. PLOS Pathog 12:e1005315 [Google Scholar]
  169. Lambotte O, Pollara J, Boufassa F, Moog C, Venet A. 169.  et al. 2013. High antibody-dependent cellular cytotoxicity responses are correlated with strong CD8 T cell viral suppressive activity but not with B57 status in HIV-1 elite controllers. PLOS ONE 8:e74855 [Google Scholar]
  170. Yates NL, Lucas JT, Nolen TL, Vandergrift NA, Soderberg KA. 170.  et al. 2011. Multiple HIV-1-specific IgG3 responses decline during acute HIV-1: implications for detection of incident HIV infection. AIDS 25:2089–97 [Google Scholar]
  171. Devito C, Broliden K, Kaul R, Svensson L, Johansen K. 171.  et al. 2000. Mucosal and plasma IgA from HIV-1-exposed uninfected individuals inhibit HIV-1 transcytosis across human epithelial cells. J. Immunol. 165:5170–76 [Google Scholar]
  172. Leeansyah E, Ganesh A, Quigley MF, Sonnerborg A, Andersson J. 172.  et al. 2013. Activation, exhaustion, and persistent decline of the antimicrobial MR1-restricted MAIT-cell population in chronic HIV-1 infection. Blood 121:1124–35 [Google Scholar]
  173. Korner C, Granoff ME, Amero MA, Sirignano MN, Vaidya SA. 173.  et al. 2014. Increased frequency and function of KIR2DL1–3+ NK cells in primary HIV-1 infection are determined by HLA-C group haplotypes. Eur. J. Immunol. 44:2938–48 [Google Scholar]
  174. Elemans M, Boelen L, Rasmussen M, Buus S, Asquith B. 174.  2017. HIV-1 adaptation to NK cell-mediated immune pressure. PLOS Pathog 13:e1006361 [Google Scholar]
  175. Alter G, Heckerman D, Schneidewind A, Fadda L, Kadie CM. 175.  et al. 2011. HIV-1 adaptation to NK-cell-mediated immune pressure. Nature 476:96–100 [Google Scholar]
  176. Young GR, Eksmond U, Salcedo R, Alexopoulou L, Stoye JP, Kassiotis G. 176.  2012. Resurrection of endogenous retroviruses in antibody-deficient mice. Nature 491:774–78 [Google Scholar]
  177. Garrison KE, Jones RB, Meiklejohn DA, Anwar N, Ndhlovu LC. 177.  et al. 2007. T cell responses to human endogenous retroviruses in HIV-1 infection. PLOS Pathog 3:e165 [Google Scholar]
  178. Zeng M, Hu Z, Shi X, Li X, Zhan X. 178.  et al. 2014. MAVS, cGAS, and endogenous retroviruses in T-independent B cell responses. Science 346:1486–92 [Google Scholar]
  179. Axer A, Halperin N. 179.  1972. Heterogenous transplant (Kiel bone) for the operative treatment of scoliosis. Arch. Orthop. Unfallchir. 72:207–14 [Google Scholar]
  180. Cheng L, Yu H, Li G, Li F, Ma J. 180.  et al. 2017. Type I interferons suppress viral replication but contribute to T cell depletion and dysfunction during chronic HIV-1 infection. JCI Insight 2:e94366 [Google Scholar]
  181. Hua S, Lecuroux C, Saez-Cirion A, Pancino G, Girault I. 181.  et al. 2014. Potential role for HIV-specific CD38/HLA-DR+ CD8+ T cells in viral suppression and cytotoxicity in HIV controllers. PLOS ONE 9:e101920 [Google Scholar]
  182. Loo CP, Snyder CM, Hill AB. 182.  2017. Blocking virus replication during acute murine cytomegalovirus infection paradoxically prolongs antigen presentation and increases the CD8+ T cell response by preventing type I IFN-dependent depletion of dendritic cells. J. Immunol. 198:383–93 [Google Scholar]
  183. Rothlin CV, Ghosh S, Zuniga EI, Oldstone MB, Lemke G. 183.  2007. TAM receptors are pleiotropic inhibitors of the innate immune response. Cell 131:1124–36 [Google Scholar]
  184. Janeway CA Jr. 184.  1989. Approaching the asymptote? Evolution and revolution in immunology. Cold Spring Harb. Symp. Quant. Biol. 54:Part 11–13 [Google Scholar]
  185. Pulendran B, Ahmed R. 185.  2011. Immunological mechanisms of vaccination. Nat. Immunol. 12:509–17 [Google Scholar]
  186. Pichlmair A, Schulz O, Tan CP, Naslund TI, Liljestrom P. 186.  et al. 2006. RIG-I-mediated antiviral responses to single-stranded RNA bearing 5′-phosphates. Science 314:997–1001 [Google Scholar]
  187. Bowie AG, Unterholzner L. 187.  2008. Viral evasion and subversion of pattern-recognition receptor signalling. Nat. Rev. Immunol. 8:911–22 [Google Scholar]
  188. Schwartz O, Marechal V, Le Gall S, Lemonnier F, Heard JM. 188.  1996. Endocytosis of major histocompatibility complex class I molecules is induced by the HIV-1 Nef protein. Nat. Med. 2:338–42 [Google Scholar]
  189. Pillai PS, Molony RD, Martinod K, Dong H, Pang IK. 189.  et al. 2016. Mx1 reveals innate pathways to antiviral resistance and lethal influenza disease. Science 352:463–66 [Google Scholar]
  190. Mellman I, Steinman RM. 190.  2001. Dendritic cells: specialized and regulated antigen processing machines. Cell 106:255–58 [Google Scholar]
  191. Courreges MC, Burzyn D, Nepomnaschy I, Piazzon I, Ross SR. 191.  2007. Critical role of dendritic cells in mouse mammary tumor virus in vivo infection. J. Virol. 81:3769–77 [Google Scholar]
  192. Duvall MG, Lore K, Blaak H, Ambrozak DA, Adams WC. 192.  et al. 2007. Dendritic cells are less susceptible to human immunodeficiency virus type 2 (HIV-2) infection than to HIV-1 infection. J. Virol. 81:13486–98 [Google Scholar]
  193. Chauveau L, Puigdomenech I, Ayinde D, Roesch F, Porrot F. 193.  et al. 2015. HIV-2 infects resting CD4+ T cells but not monocyte-derived dendritic cells. Retrovirology 12:2 [Google Scholar]
  194. Chauveau L, Donahue DA, Monel B, Porrot F, Bruel T. 194.  et al. 2017. HIV fusion in dendritic cells occurs mainly at the surface and is limited by low CD4 levels. J. Virol. 21:e01248–17 [Google Scholar]
  195. Honke N, Shaabani N, Cadeddu G, Sorg UR, Zhang DE. 195.  et al. 2011. Enforced viral replication activates adaptive immunity and is essential for the control of a cytopathic virus. Nat. Immunol. 13:51–57 [Google Scholar]
  196. Baldauf HM, Stegmann L, Schwarz SM, Ambiel I, Trotard M. 196.  et al. 2017. Vpx overcomes a SAMHD1-independent block to HIV reverse transcription that is specific to resting CD4 T cells. PNAS 114:2729–34 [Google Scholar]
  197. Yu H, Usmani SM, Borch A, Kramer J, Sturzel CM. 197.  et al. 2013. The efficiency of Vpx-mediated SAMHD1 antagonism does not correlate with the potency of viral control in HIV-2-infected individuals. Retrovirology 10:27 [Google Scholar]
  198. Shingai M, Welbourn S, Brenchley JM, Acharya P, Miyagi E. 198.  et al. 2015. The expression of functional Vpx during pathogenic SIVmac infections of rhesus macaques suppresses SAMHD1 in CD4+ memory T cells. PLOS Pathog 11:e1004928 [Google Scholar]
  199. Gramberg T, Kahle T, Bloch N, Wittmann S, Mullers E. 199.  et al. 2013. Restriction of diverse retroviruses by SAMHD1. Retrovirology 10:26 [Google Scholar]
  200. Varol C, Vallon-Eberhard A, Elinav E, Aychek T, Shapira Y. 200.  et al. 2009. Intestinal lamina propria dendritic cell subsets have different origin and functions. Immunity 31:502–12 [Google Scholar]
  201. Segura E, Valladeau-Guilemond J, Donnadieu MH, Sastre-Garau X, Soumelis V, Amigorena S. 201.  2012. Characterization of resident and migratory dendritic cells in human lymph nodes. J. Exp. Med. 209:653–60 [Google Scholar]
  202. Hasenkrug KJ, Dittmer U. 202.  2007. Immune control and prevention of chronic Friend retrovirus infection. Front. Biosci. 12:1544–51 [Google Scholar]
  203. Browne EP, Littman DR. 203.  2009. Myd88 is required for an antibody response to retroviral infection. PLOS Pathog 5:e1000298 [Google Scholar]
  204. Kirchhoff F. 204.  2010. Immune evasion and counteraction of restriction factors by HIV-1 and other primate lentiviruses. Cell Host Microbe 8:55–67 [Google Scholar]
  205. Lim ES, Fregoso OI, McCoy CO, Matsen FA, Malik HS, Emerman M. 205.  2012. The ability of primate lentiviruses to degrade the monocyte restriction factor SAMHD1 preceded the birth of the viral accessory protein Vpx. Cell Host Microbe 11:194–204 [Google Scholar]
  206. Sun L, Wu J, Du F, Chen X, Chen ZJ. 206.  2013. Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway. Science 339:786–91 [Google Scholar]
  207. Descours B, Petitjean G, Lopez-Zaragoza JL, Bruel T, Raffel R. 207.  et al. 2017. CD32a is a marker of a CD4 T-cell HIV reservoir harbouring replication-competent proviruses. Nature 543:564–67 [Google Scholar]
  208. Connick E, Mattila T, Folkvord JM, Schlichtemeier R, Meditz AL. 208.  et al. 2007. CTL fail to accumulate at sites of HIV-1 replication in lymphoid tissue. J. Immunol. 178:6975–83 [Google Scholar]
  209. Petrovas C, Ferrando-Martinez S, Gerner MY, Casazza JP, Pegu A. 209.  et al. 2017. Follicular CD8 T cells accumulate in HIV infection and can kill infected cells in vitro via bispecific antibodies. Sci. Transl. Med. 9:eaag2285 [Google Scholar]
  210. Perreau M, Savoye AL, De Crignis E, Corpataux JM, Cubas R. 210.  et al. 2013. Follicular helper T cells serve as the major CD4 T cell compartment for HIV-1 infection, replication, and production. J. Exp. Med. 210:143–56 [Google Scholar]
  211. Stetson DB, Ko JS, Heidmann T, Medzhitov R. 211.  2008. Trex1 prevents cell-intrinsic initiation of autoimmunity. Cell 134:587–98 [Google Scholar]
  212. Crow YJ, Manel N. 212.  2015. Aicardi-Goutières syndrome and the type I interferonopathies. Nat. Rev. Immunol. 15:429–40 [Google Scholar]
  213. Vance RE, Isberg RR, Portnoy DA. 213.  2009. Patterns of pathogenesis: discrimination of pathogenic and nonpathogenic microbes by the innate immune system. Cell Host Microbe 6:10–21 [Google Scholar]
  214. Galao RP, Le Tortorec A Pickering S, Kueck T, Neil SJ. 214.  2012. Innate sensing of HIV-1 assembly by Tetherin induces NFκB-dependent proinflammatory responses. Cell Host Microbe 12:633–44 [Google Scholar]
  215. Chae E, Tran DT, Weigel D. 215.  2016. Cooperation and conflict in the plant immune system. PLOS Pathog 12:e1005452 [Google Scholar]
  216. Baldauf HM, Pan X, Erikson E, Schmidt S, Daddacha W. 216.  et al. 2012. SAMHD1 restricts HIV-1 infection in resting CD4+ T cells. Nat. Med. 18:1682–87 [Google Scholar]
  217. Parrish NF, Gao F, Li H, Giorgi EE, Barbian HJ. 217.  et al. 2013. Phenotypic properties of transmitted founder HIV-1. PNAS 110:6626–33 [Google Scholar]
  218. Sandler NG, Bosinger SE, Estes JD, Zhu RT, Tharp GK. 218.  et al. 2014. Type I interferon responses in rhesus macaques prevent SIV infection and slow disease progression. Nature 511:601–5 [Google Scholar]
  219. Deeks SG, Kitchen CM, Liu L, Guo H, Gascon R. 219.  et al. 2004. Immune activation set point during early HIV infection predicts subsequent CD4+ T-cell changes independent of viral load. Blood 104:942–47 [Google Scholar]
  220. Wherry EJ, Ha SJ, Kaech SM, Haining WN, Sarkar S. 220.  et al. 2007. Molecular signature of CD8+ T cell exhaustion during chronic viral infection. Immunity 27:670–84 [Google Scholar]
  221. Day CL, Kaufmann DE, Kiepiela P, Brown JA, Moodley ES. 221.  et al. 2006. PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression. Nature 443:350–54 [Google Scholar]

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error