Advertisement

HIV-1 Latency pp 111-130 | Cite as

SIV Latency in Macrophages in the CNS

  • Lucio Gama
  • Celina Abreu
  • Erin N. Shirk
  • Suzanne E. Queen
  • Sarah E. Beck
  • Kelly A. Metcalf Pate
  • Brandon T. Bullock
  • M. Christine Zink
  • Joseph L. Mankowski
  • Janice E. Clements
Chapter
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 417)

Abstract

Lentiviruses infect myeloid cells, leading to acute infection followed by persistent/latent infections not cleared by the host immune system. HIV and SIV are lentiviruses that infect CD4+ lymphocytes in addition to myeloid cells in blood and tissues. HIV infection of myeloid cells in brain, lung, and heart causes tissue-specific diseases that are mostly observed during severe immunosuppression, when the number of circulating CD4+ T cells declines to exceeding low levels. Antiretroviral therapy (ART) controls viral replication but does not successfully eliminate latent virus, which leads to viral rebound once ART is interrupted. HIV latency in CD4+ lymphocytes is the main focus of research and concern when HIV eradication efforts are considered. However, myeloid cells in tissues are long-lived and have not been routinely examined as a potential reservoir. Based on a quantitative viral outgrowth assay (QVOA) designed to evaluate latently infected CD4+ lymphocytes, a similar protocol was developed for the assessment of latently infected myeloid cells in blood and tissues. Using an SIV ART model, it was demonstrated that myeloid cells in blood and brain harbor latent SIV that can be reactivated and produce infectious virus in vitro, demonstrating that myeloid cells have the potential to be an additional latent reservoir of HIV that should be considered during HIV eradication strategies.

Notes

Acknowledgements

These studies were funded by NIH awards R01NS089482, R01NS077869, P40OD0131117, R01NS055651, R56AI118753, R01AI127142, P01MH070306, P01AI131306, and the Johns Hopkins University Center for AIDS Research P30AI094189.

Anti-retroviral compounds for these studies were kindly donated by Gilead, ViiV Healthcare, Bristol-Meyers Squibb, Merck, Abbvie, Janssen, and Roche. These studies were supported by the excellent technical staff in the Retrovirus Lab at Johns Hopkins.

References

  1. Abreu CM, Price SL, Shirk EN, Cunha RD, Pianowski LF, Clements JE, Tanuri A, Gama L (2014) Dual role of novel ingenol derivatives from Euphorbia tirucalli in HIV replication: inhibition of de novo infection and activation of viral LTR. PLoS ONE 9:e97257PubMedPubMedCentralGoogle Scholar
  2. Alfano M, Graziano F, Genovese L, Poli G (2013) Macrophage polarization at the crossroad between HIV-1 infection and cancer development. Arterioscler Thromb Vasc Biol 33:1145–1152PubMedGoogle Scholar
  3. Anderson AM, Munoz-Moreno JA, McClernon DR, Ellis RJ, Cookson D, Clifford DB, Collier C, Gelman BB, Marra CM, McArthur JC, McCutchan JA, Morgello S, Sacktor N, Simpson DM, Franklin DR, Heaton RK, Grant I, Letendre SL, Group C (2017) Prevalence and correlates of persistent HIV-1 RNA in cerebrospinal fluid during antiretroviral therapy. J Infect Dis 215:105–113PubMedGoogle Scholar
  4. Arnaout MA (1990) Structure and function of the leukocyte adhesion molecules CD11/CD18. Blood 75:1037–1050PubMedGoogle Scholar
  5. Avalos CR, Price SL, Forsyth ER, Pin JN, Shirk EN, Bullock BT, Queen SE, Li M, Gellerup D, O’Connor SL, Zink MC, Mankowski JL, Gama L, Clements JE (2016) Quantitation of productively infected monocytes and macrophages of simian immunodeficiency virus-infected macaques. J Virol 90:5643–5656PubMedPubMedCentralGoogle Scholar
  6. Avalos CR, Abreu CM, Queen SE, Li M, Price S, Shirk EN, Engle EL, Forsyth E, Bullock BT, Mac Gabhann F, Wietgrefe SW, Haase AT, Zink MC, Mankowski JL, Clements JE, Gama L (2017) Brain macrophages in simian immunodeficiency virus-infected, antiretroviral-suppressed macaques: a functional latent reservoir. MBio 8Google Scholar
  7. Barber SA, Gama L, Dudaronek JM, Voelker T, Tarwater PM, Clements JE (2006a) Mechanism for the establishment of transcriptional HIV latency in the brain in a simian immunodeficiency virus-macaque model. J Infect Dis 193:963–970PubMedGoogle Scholar
  8. Barber SA, Gama L, Li M, Voelker T, Anderson JE, Zink MC, Tarwater PM, Carruth LM, Clements JE (2006b) Longitudinal analysis of simian immunodeficiency virus (SIV) replication in the lungs: compartmentalized regulation of SIV. J Infect Dis 194:931–938PubMedGoogle Scholar
  9. Barre-Sinoussi F, Chermann JC, Rey F, Nugeyre MT, Chamaret S, Gruest J, Dauguet C, Axler-Blin C, Vezinet-Brun F, Rouzioux C, Rozenbaum W, Montagnier L (1983) Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). Science 220:868–871Google Scholar
  10. Brinkmann R, Schwinn A, Muller J, Stahl-Hennig C, Coulibaly C, Hunsmann G, Czub S, Rethwilm A, Dorries R, ter Meulen V (1993) In vitro and in vivo infection of rhesus monkey microglial cells by simian immunodeficiency virus. Virology 195:561–568PubMedGoogle Scholar
  11. Burdo TH, Lackner A, Williams KC (2013) Monocyte/macrophages and their role in HIV neuropathogenesis. Immunol Rev 254:102–113PubMedPubMedCentralGoogle Scholar
  12. Cai Y, Sugimoto C, Arainga M, Alvarez X, Didier ES, Kuroda MJ (2014) In vivo characterization of alveolar and interstitial lung macrophages in rhesus macaques: implications for understanding lung disease in humans. J Immunol 192:2821–2829PubMedPubMedCentralGoogle Scholar
  13. Canestri A, Lescure FX, Jaureguiberry S, Moulignier A, Amiel C, Marcelin AG, Peytavin G, Tubiana R, Pialoux G, Katlama C (2010) Discordance between cerebral spinal fluid and plasma HIV replication in patients with neurological symptoms who are receiving suppressive antiretroviral therapy. Clin Infect Dis 50:773–778PubMedGoogle Scholar
  14. Cassetta L, Kajaste-Rudnitski A, Coradin T, Saba E, Della Chiara G, Barbagallo M, Graziano F, Alfano M, Cassol E, Vicenzi E, Poli G (2013) M1 polarization of human monocyte-derived macrophages restricts pre and postintegration steps of HIV-1 replication. AIDS 27:1847–1856PubMedGoogle Scholar
  15. Chen R, Le Rouzic E, Kearney JA, Mansky LM, Benichou S (2004) Vpr-mediated incorporation of UNG2 into HIV-1 particles is required to modulate the virus mutation rate and for replication in macrophages. J Biol Chem 279:28419–28425PubMedGoogle Scholar
  16. Cherry JD, Olschowka JA, O’Banion MK (2014) Neuroinflammation and M2 microglia: the good, the bad, and the inflamed. J Neuroinflammation 11:98PubMedPubMedCentralGoogle Scholar
  17. Chiodi F, Albert J, Olausson E, Norkrans G, Hagberg L, Sonnerborg A, Asjo B, Fenyo EM (1988) Isolation frequency of human immunodeficiency virus from cerebrospinal fluid and blood of patients with varying severity of HIV infection. AIDS Res Hum Retroviruses 4:351–358PubMedGoogle Scholar
  18. Clements JE, Babas T, Mankowski JL, Suryanarayana K, Piatak M Jr, Tarwater PM, Lifson JD, Zink MC (2002a) The central nervous system as a reservoir for simian immunodeficiency virus (SIV): steady-state levels of SIV DNA in brain from acute through asymptomatic infection. J Infect Dis 186:905–913PubMedGoogle Scholar
  19. Clements JE, Babas T, Mankowski JL, Suryanarayana K, Piatak M Jr, Tarwater PM, Lifson JD, Zink MC (2002b) The central nervous system as a reservoir for simian immunodeficiency virus (SIV): steady-state levels of SIV DNA in brain from acute through asymptomatic infection. J Infect Dis 186:905–913PubMedGoogle Scholar
  20. Cobos Jimenez V, Booiman T, de Taeye SW, van Dort KA, Rits MA, Hamann J, Kootstra NA (2012) Differential expression of HIV-1 interfering factors in monocyte-derived macrophages stimulated with polarizing cytokines or interferons. Sci Rep 2:763PubMedPubMedCentralGoogle Scholar
  21. Cosenza MA, Zhao ML, Si Q, Lee SC (2002) Human brain parenchymal microglia express CD14 and CD45 and are productively infected by HIV-1 in HIV-1 encephalitis. Brain Pathol 12:442–455PubMedPubMedCentralGoogle Scholar
  22. Craig LE, Sheffer D, Meyer AL, Hauer D, Lechner F, Peterhans E, Adams RJ, Clements JE, Narayan O, Zink MC (1997) Pathogenesis of ovine lentiviral encephalitis: derivation of a neurovirulent strain by in vivo passage. J Neurovirol 3:417–427PubMedGoogle Scholar
  23. Dar RD, Hosmane NN, Arkin MR, Siliciano RF, Weinberger LS (2014) Screening for noise in gene expression identifies drug synergies. Science 344:1392–1396PubMedPubMedCentralGoogle Scholar
  24. Davis MJ, Tsang TM, Qiu Y, Dayrit JK, Freij JB, Huffnagle GB, Olszewski MA (2013) Macrophage M1/M2 polarization dynamically adapts to changes in cytokine microenvironments in Cryptococcus neoformans infection. MBio 4:e00264–00213Google Scholar
  25. Descombes P, Schibler U (1991) A liver-enriched transcriptional activator protein, LAP, and a transcriptional inhibitory protein, LIP, are translated from the same mRNA. Cell 67:569–579PubMedGoogle Scholar
  26. Dinoso JB, Rabi SA, Blankson JN, Gama L, Mankowski JL, Siliciano RF, Zink MC, Clements JE (2009) A simian immunodeficiency virus-infected macaque model to study viral reservoirs that persist during highly active antiretroviral therapy. J Virol 83:9247–9257PubMedPubMedCentralGoogle Scholar
  27. Eden A, Fuchs D, Hagberg L, Nilsson S, Spudich S, Svennerholm B, Price RW, Gisslen M (2010) HIV-1 viral escape in cerebrospinal fluid of subjects on suppressive antiretroviral treatment. J Infect Dis 202:1819–1825PubMedPubMedCentralGoogle Scholar
  28. Epstein LG, Sharer LR, Cho ES, Myenhofer M, Navia B, Price RW (1984) HTLV-III/LAV-like retrovirus particles in the brains of patients with AIDS encephalopathy. AIDS Res 1:447–454PubMedGoogle Scholar
  29. Francella N, Elliott ST, Yi Y, Gwyn SE, Ortiz AM, Li B, Silvestri G, Paiardini M, Derdeyn CA, Collman RG (2013) Decreased plasticity of coreceptor use by CD4-independent SIV Envs that emerge in vivo. Retrovirology 10:133PubMedPubMedCentralGoogle Scholar
  30. Gama L, Abreu CM, Shirk EN, Price SL, Li M, Laird GM, Pate KA, Wietgrefe SW, O’Connor SL, Pianowski L, Haase AT, Van Lint C, Siliciano RF, Clements JE, Group L-SS (2017) Reactivation of simian immunodeficiency virus reservoirs in the brain of virally suppressed macaques. AIDS 31:5–14PubMedPubMedCentralGoogle Scholar
  31. Gartner S, Markovits P, Markovitz DM, Kaplan MH, Gallo RC, Popovic M (1986) The role of mononuclear phagocytes in HTLV-III/LAV infection. Science 233:215–219PubMedGoogle Scholar
  32. Gautier EL, Shay T, Miller J, Greter M, Jakubzick C, Ivanov S, Helft J, Chow A, Elpek KG, Gordonov S, Mazloom AR, Ma’ayan A, Chua WJ, Hansen TH, Turley SJ, Merad M, Randolph GJ, Immunological Genome C (2012) Gene-expression profiles and transcriptional regulatory pathways that underlie the identity and diversity of mouse tissue macrophages. Nat Immunol 13:1118–1128PubMedPubMedCentralGoogle Scholar
  33. Gendelman HE, Narayan O, Molineaux S, Clements JE, Ghotbi Z (1985a) Slow, persistent replication of lentiviruses: role of tissue macrophages and macrophage precursors in bone marrow. Proc Natl Acad Sci U S A 82:7086–7090PubMedPubMedCentralGoogle Scholar
  34. Gendelman HE, Moench TR, Narayan O, Griffin DE, Clements JE (1985b) A double labeling technique for performing immunocytochemistry and in situ hybridization in virus infected cell cultures and tissues. J Virol Methods 11:93–103PubMedGoogle Scholar
  35. Gendelman HE, Narayan O, Kennedy-Stoskopf S, Kennedy PG, Ghotbi Z, Clements JE, Stanley J, Pezeshkpour G (1986) Tropism of sheep lentiviruses for monocytes: susceptibility to infection and virus gene expression increase during maturation of monocytes to macrophages. J Virol 58:67–74PubMedPubMedCentralGoogle Scholar
  36. Ginhoux F, Jung S (2014) Monocytes and macrophages: developmental pathways and tissue homeostasis. Nat Rev Immunol 14:392–404PubMedGoogle Scholar
  37. Gonda MA, Wong-Staal F, Gallo RC, Clements JE, Narayan O, Gilden RV (1985) Sequence homology and morphologic similarity of HTLV-III and visna virus, a pathogenic lentivirus. Science 227:173–177PubMedGoogle Scholar
  38. Gonda MA, Braun MJ, Clements JE, Pyper JM, Wong-Staal F, Gallo RC, Gilden RV (1986) Human T-cell lymphotropic virus type III shares sequence homology with a family of pathogenic lentiviruses. Proc Natl Acad Sci U S A 83:4007–4011PubMedPubMedCentralGoogle Scholar
  39. Gordon S (2003) Alternative activation of macrophages. Nat Rev Immunol 3:23–35PubMedGoogle Scholar
  40. Gordon S, Taylor PR (2005) Monocyte and macrophage heterogeneity. Nat Rev Immunol 5:953–964PubMedGoogle Scholar
  41. Gorry PR, Churchill M, Crowe SM, Cunningham AL, Gabuzda D (2005) Pathogenesis of macrophage tropic HIV-1. Curr HIV Res 3:53–60PubMedGoogle Scholar
  42. Gottlieb MS, Schroff R, Schanker HM, Weisman JD, Fan PT, Wolf RA, Saxon A (1981) Pneumocystis carinii pneumonia and mucosal candidiasis in previously healthy homosexual men: evidence of a new acquired cellular immunodeficiency. N Engl J Med 305:1425–1431PubMedGoogle Scholar
  43. Guilliams M, Ginhoux F, Jakubzick C, Naik SH, Onai N, Schraml BU, Segura E, Tussiwand R, Yona S (2014) Dendritic cells, monocytes and macrophages: a unified nomenclature based on ontogeny. Nat Rev Immunol 14:571–578PubMedPubMedCentralGoogle Scholar
  44. Hashimoto D, Chow A, Noizat C, Teo P, Beasley MB, Leboeuf M, Becker CD, See P, Price J, Lucas D, Greter M, Mortha A, Boyer SW, Forsberg EC, Tanaka M, van Rooijen N, Garcia-Sastre A, Stanley ER, Ginhoux F, Frenette PS, Merad M (2013) Tissue-resident macrophages self-maintain locally throughout adult life with minimal contribution from circulating monocytes. Immunity 38:792–804PubMedGoogle Scholar
  45. Hearps AC, Martin GE, Angelovich TA, Cheng WJ, Maisa A, Landay AL, Jaworowski A, Crowe SM (2012) Aging is associated with chronic innate immune activation and dysregulation of monocyte phenotype and function. Aging Cell 11:867–875PubMedGoogle Scholar
  46. Heaton RK, Clifford DB, Franklin DR Jr., Woods SP, Ake C, Vaida F, Ellis RJ, Letendre SL, Marcotte TD, Atkinson JH, Rivera-Mindt M, Vigil OR, Taylor MJ, Collier AC, Marra CM, Gelman BB, McArthur JC, Morgello S, Simpson DM, McCutchan JA, Abramson I, Gamst A, Fennema-Notestine C, Jernigan TL, Wong J, Grant I, Group C (2010) HIV-associated neurocognitive disorders persist in the era of potent antiretroviral therapy: CHARTER study. Neurology 75:2087–2096PubMedPubMedCentralGoogle Scholar
  47. Heaton RK, Franklin DR, Ellis RJ, McCutchan JA, Letendre SL, Leblanc S, Corkran SH, Duarte NA, Clifford DB, Woods SP, Collier AC, Marra CM, Morgello S, Mindt MR, Taylor MJ, Marcotte TD, Atkinson JH, Wolfson T, Gelman BB, McArthur JC, Simpson DM, Abramson I, Gamst A, Fennema-Notestine C, Jernigan TL, Wong J, Grant I, Group C, Group H (2011) HIV-associated neurocognitive disorders before and during the era of combination antiretroviral therapy: differences in rates, nature, and predictors. J Neurovirol 17:3–16PubMedGoogle Scholar
  48. Henderson AJ, Calame KL (1997) CCAAT/enhancer binding protein (C/EBP) sites are required for HIV-1 replication in primary macrophages but not CD4(+) T cells. Proc Natl Acad Sci U S A 94:8714–8719PubMedPubMedCentralGoogle Scholar
  49. Henderson AJ, Zou X, Calame KL (1995) C/EBP proteins activate transcription from the human immunodeficiency virus type 1 long terminal repeat in macrophages/monocytes. J Virol 69:5337–5344PubMedPubMedCentralGoogle Scholar
  50. Henderson AJ, Connor RI, Calame KL (1996) C/EBP activators are required for HIV-1 replication and proviral induction in monocytic cell lines. Immunity 5:91–101PubMedGoogle Scholar
  51. Henrich TJ, Hanhauser E, Marty FM, Sirignano MN, Keating S, Lee TH, Robles YP, Davis BT, Li JZ, Heisey A, Hill AL, Busch MP, Armand P, Soiffer RJ, Altfeld M, Kuritzkes DR (2014) Antiretroviral-free HIV-1 remission and viral rebound after allogeneic stem cell transplantation: report of 2 cases. Ann Intern Med 161:319–327PubMedPubMedCentralGoogle Scholar
  52. Ho DD, Rota TR, Schooley RT, Kaplan JC, Allan JD, Groopman JE, Resnick L, Felsenstein D, Andrews CA, Hirsch MS (1985) Isolation of HTLV-III from cerebrospinal fluid and neural tissues of patients with neurologic syndromes related to the acquired immunodeficiency syndrome. N Engl J Med 313:1493–1497PubMedGoogle Scholar
  53. Honda Y, Rogers L, Nakata K, Zhao BY, Pine R, Nakai Y, Kurosu K, Rom WN, Weiden M (1998) Type I interferon induces inhibitory 16-kD CCAAT/ enhancer binding protein (C/EBP)beta, repressing the HIV-1 long terminal repeat in macrophages: pulmonary tuberculosis alters C/EBP expression, enhancing HIV-1 replication. J Exp Med 188:1255–1265PubMedPubMedCentralGoogle Scholar
  54. Igarashi T, Imamichi H, Brown CR, Hirsch VM, Martin MA (2003) The emergence and characterization of macrophage-tropic SIV/HIV chimeric viruses (SHIVs) present in CD4+ T cell-depleted rhesus monkeys. J Leukoc Biol 74:772–780PubMedGoogle Scholar
  55. Karita E, Nkengasong JN, Willems B, Vanham G, Fransen K, Heyndrickx L, Janssens W, Piot P, van der Groen G (1997) Macrophage-tropism of HIV-1 isolates of different genetic subtypes. AIDS 11:1303–1304PubMedGoogle Scholar
  56. Kennedy PG (1988) Neurological complications of human immunodeficiency virus infection. Postgrad Med J 64:180–187PubMedPubMedCentralGoogle Scholar
  57. Kinoshita S, Su L, Amano M, Timmerman LA, Kaneshima H, Nolan GP (1997) The T cell activation factor NF-ATc positively regulates HIV-1 replication and gene expression in T cells. Immunity 6:235–244PubMedGoogle Scholar
  58. Kobayashi K, Imagama S, Ohgomori T, Hirano K, Uchimura K, Sakamoto K, Hirakawa A, Takeuchi H, Suzumura A, Ishiguro N, Kadomatsu K (2013) Minocycline selectively inhibits M1 polarization of microglia. Cell Death Dis 4:e525PubMedPubMedCentralGoogle Scholar
  59. Kumar N, Chahroudi A, Silvestri G (2016) Animal models to achieve an HIV cure. Curr Opin HIV AIDS 11:432–441PubMedPubMedCentralGoogle Scholar
  60. Lamers SL, Gray RR, Salemi M, Huysentruyt LC, McGrath MS (2011) HIV-1 phylogenetic analysis shows HIV-1 transits through the meninges to brain and peripheral tissues. Infect Genet Evol 11:31–37PubMedGoogle Scholar
  61. Mankowski JL, Flaherty MT, Spelman JP, Hauer DA, Didier PJ, Amedee AM, Murphey-Corb M, Kirstein LM, Munoz A, Clements JE, Zink MC (1997) Pathogenesis of simian immunodeficiency virus encephalitis: viral determinants of neurovirulence. J Virol 71:6055–6060PubMedPubMedCentralGoogle Scholar
  62. Mankowski JL, Carter DL, Spelman JP, Nealen ML, Maughan KR, Kirstein LM, Didier PJ, Adams RJ, Murphey-Corb M, Zink MC (1998) Pathogenesis of simian immunodeficiency virus pneumonia: an immunopathological response to virus. Am J Pathol 153:1123–1130PubMedPubMedCentralGoogle Scholar
  63. Martinez FO, Gordon S (2014) The M1 and M2 paradigm of macrophage activation: time for reassessment. F1000Prime Rep 6:13PubMedPubMedCentralGoogle Scholar
  64. Martinez FO, Gordon S, Locati M, Mantovani A (2006) Transcriptional profiling of the human monocyte-to-macrophage differentiation and polarization: new molecules and patterns of gene expression. J Immunol 177:7303–7311PubMedGoogle Scholar
  65. Masur H, Michelis MA, Greene JB, Onorato I, Stouwe RA, Holzman RS, Wormser G, Brettman L, Lange M, Murray HW, Cunningham-Rundles S (1981) An outbreak of community-acquired Pneumocystis carinii pneumonia: initial manifestation of cellular immune dysfunction. N Engl J Med 305:1431–1438PubMedGoogle Scholar
  66. McArthur JC, Steiner J, Sacktor N, Nath A (2010) Human immunodeficiency virus-associated neurocognitive disorders: Mind the gap. Ann Neurol 67:699–714PubMedGoogle Scholar
  67. Mulder R, Banete A, Basta S (2014) Spleen-derived macrophages are readily polarized into classically activated (M1) or alternatively activated (M2) states. Immunobiology 219:737–745PubMedGoogle Scholar
  68. Narayan O, Kennedy-Stoskopf S, Sheffer D, Griffin DE, Clements JE (1983) Activation of caprine arthritis-encephalitis virus expression during maturation of monocytes to macrophages. Infect Immun 41:67–73PubMedPubMedCentralGoogle Scholar
  69. Neuen-Jacob E, Arendt G, Wendtland B, Jacob B, Schneeweis M, Wechsler W (1993) Frequency and topographical distribution of CD68-positive macrophages and HIV-1 core proteins in HIV-associated brain lesions. Clin Neuropathol 12:315–324PubMedGoogle Scholar
  70. Okabe Y, Medzhitov R (2014) Tissue-specific signals control reversible program of localization and functional polarization of macrophages. Cell 157:832–844PubMedPubMedCentralGoogle Scholar
  71. Orihuela R, McPherson CA, Harry GJ (2016) Microglial M1/M2 polarization and metabolic states. Br J Pharmacol 173:649–665PubMedPubMedCentralGoogle Scholar
  72. Ortiz AM, Klatt NR, Li B, Yi Y, Tabb B, Hao XP, Sternberg L, Lawson B, Carnathan PM, Cramer EM, Engram JC, Little DM, Ryzhova E, Gonzalez-Scarano F, Paiardini M, Ansari AA, Ratcliffe S, Else JG, Brenchley JM, Collman RG, Estes JD, Derdeyn CA, Silvestri G (2011) Depletion of CD4(+) T cells abrogates post-peak decline of viremia in SIV-infected rhesus macaques. J Clin Invest 121:4433–4445PubMedPubMedCentralGoogle Scholar
  73. Peluso R, Haase A, Stowring L, Edwards M, Ventura P (1985) A Trojan Horse mechanism for the spread of visna virus in monocytes. Virology 147:231–236PubMedGoogle Scholar
  74. Pierson T, McArthur J, Siliciano RF (2000) Reservoirs for HIV-1: mechanisms for viral persistence in the presence of antiviral immune responses and antiretroviral therapy. Annu Rev Immunol 18:665–708PubMedGoogle Scholar
  75. Pollack RA, Jones RB, Pertea M, Bruner KM, Martin AR, Thomas AS, Capoferri AA, Beg SA, Huang SH, Karandish S, Hao H, Halper-Stromberg E, Yong PC, Kovacs C, Benko E, Siliciano RF, Ho YC (2017) Defective HIV-1 proviruses are expressed and can be recognized by cytotoxic T lymphocytes, which shape the proviral landscape. Cell Host Microbe 21(494–506):e494Google Scholar
  76. Popovic M, Sarngadharan MG, Read E, Gallo RC (1984) Detection, isolation, and continuous production of cytopathic retroviruses (HTLV-III) from patients with AIDS and pre-AIDS. Science 224:497–500Google Scholar
  77. Qin Y, Sun X, Shao X, Cheng C, Feng J, Sun W, Gu D, Liu W, Xu F, Duan Y (2015) Macrophage-microglia networks drive M1 microglia polarization after mycobacterium infection. Inflammation 38:1609–1616PubMedGoogle Scholar
  78. Rainho JN, Martins MA, Cunyat F, Watkins IT, Watkins DI, Stevenson M (2015) Nef is dispensable for resistance of simian immunodeficiency virus-infected macrophages to CD8+T cell killing. J Virol 89:10625–10636PubMedPubMedCentralGoogle Scholar
  79. Rao VR, Ruiz AP, Prasad VR (2014) Viral and cellular factors underlying neuropathogenesis in HIV associated neurocognitive disorders (HAND). AIDS Res Ther 11:13PubMedPubMedCentralGoogle Scholar
  80. Rappaport J, Volsky DJ (2015) Role of the macrophage in HIV-associated neurocognitive disorders and other comorbidities in patients on effective antiretroviral treatment. J Neurovirol 21:235–241PubMedPubMedCentralGoogle Scholar
  81. Redente EF, Higgins DM, Dwyer-Nield LD, Orme IM, Gonzalez-Juarrero M, Malkinson AM (2010) Differential polarization of alveolar macrophages and bone marrow-derived monocytes following chemically and pathogen-induced chronic lung inflammation. J Leukoc Biol 88:159–168PubMedPubMedCentralGoogle Scholar
  82. Rosenbloom DI, Elliott O, Hill AL, Henrich TJ, Siliciano JM, Siliciano RF (2015) Designing and interpreting limiting dilution assays: general principles and applications to the latent reservoir for human immunodeficiency virus-1. Open Forum Infect Dis 2:ofv123Google Scholar
  83. Schulz C, Gomez Perdiguero E, Chorro L, Szabo-Rogers H, Cagnard N, Kierdorf K, Prinz M, Wu B, Jacobsen SE, Pollard JW, Frampton J, Liu KJ, Geissmann F (2012) A lineage of myeloid cells independent of Myb and hematopoietic stem cells. Science 336:86–90PubMedPubMedCentralGoogle Scholar
  84. Sgarbanti M, Remoli AL, Marsili G, Ridolfi B, Borsetti A, Perrotti E, Orsatti R, Ilari R, Sernicola L, Stellacci E, Ensoli B, Battistini A (2008) IRF-1 is required for full NF-kappaB transcriptional activity at the human immunodeficiency virus type 1 long terminal repeat enhancer. J Virol 82:3632–3641PubMedPubMedCentralGoogle Scholar
  85. Sharova N, Wu Y, Zhu X, Stranska R, Kaushik R, Sharkey M, Stevenson M (2008) Primate lentiviral Vpx commandeers DDB1 to counteract a macrophage restriction. PLoS Pathog 4:e1000057PubMedPubMedCentralGoogle Scholar
  86. Shaw GM, Harper ME, Hahn BH, Epstein LG, Gajdusek DC, Price RW, Navia BA, Petito CK, O’Hara CJ, Groopman JE et al (1985) HTLV-III infection in brains of children and adults with AIDS encephalopathy. Science 227:177–182PubMedGoogle Scholar
  87. Sirois M, Robitaille L, Allary R, Shah M, Woelk CH, Estaquier J, Corbeil J (2011) TRAF6 and IRF7 control HIV replication in macrophages. PLoS ONE 6:e28125PubMedPubMedCentralGoogle Scholar
  88. Spudich SS, Nilsson AC, Lollo ND, Liegler TJ, Petropoulos CJ, Deeks SG, Paxinos EE, Price RW (2005) Cerebrospinal fluid HIV infection and pleocytosis: relation to systemic infection and antiretroviral treatment. BMC Infect Dis 5:98PubMedPubMedCentralGoogle Scholar
  89. Tamoutounour S, Guilliams M, Montanana Sanchis F, Liu H, Terhorst D, Malosse C, Pollet E, Ardouin L, Luche H, Sanchez C, Dalod M, Malissen B, Henri S (2013) Origins and functional specialization of macrophages and of conventional and monocyte-derived dendritic cells in mouse skin. Immunity 39:925–938PubMedGoogle Scholar
  90. Tong-Starksen SE, Luciw PA, Peterlin BM (1987) Human immunodeficiency virus long terminal repeat responds to T-cell activation signals. Proc Natl Acad Sci U S A 84:6845–6849PubMedPubMedCentralGoogle Scholar
  91. Vojnov L, Martins MA, Bean AT, Veloso de Santana MG, Sacha JB, Wilson NA, Bonaldo MC, Galler R, Stevenson M, Watkins DI (2012) The majority of freshly sorted simian immunodeficiency virus (SIV)-specific CD8(+) T cells cannot suppress viral replication in SIV-infected macrophages. J Virol 86:4682–4687PubMedPubMedCentralGoogle Scholar
  92. Wan J, Benkdane M, Teixeira-Clerc F, Bonnafous S, Louvet A, Lafdil F, Pecker F, Tran A, Gual P, Mallat A, Lotersztajn S, Pavoine C (2014) M2 Kupffer cells promote M1 Kupffer cell apoptosis: a protective mechanism against alcoholic and nonalcoholic fatty liver disease. Hepatology 59:130–142Google Scholar
  93. Weiden M, Tanaka N, Qiao Y, Zhao BY, Honda Y, Nakata K, Canova A, Levy DE, Rom WN, Pine R (2000) Differentiation of monocytes to macrophages switches the Mycobacterium tuberculosis effect on HIV-1 replication from stimulation to inhibition: modulation of interferon response and CCAAT/enhancer binding protein beta expression. J Immunol 165:2028–2039PubMedGoogle Scholar
  94. Weinberger LS, Burnett JC, Toettcher JE, Arkin AP, Schaffer DV (2005) Stochastic gene expression in a lentiviral positive-feedback loop: HIV-1 Tat fluctuations drive phenotypic diversity. Cell 122:169–182PubMedGoogle Scholar
  95. Westmoreland SV, Converse AP, Hrecka K, Hurley M, Knight H, Piatak M, Lifson J, Mansfield KG, Skowronski J, Desrosiers RC (2014) SIV vpx is essential for macrophage infection but not for development of AIDS. PLoS ONE 9:e84463PubMedPubMedCentralGoogle Scholar
  96. Whitney JB, Hill AL, Sanisetty S, Penaloza-MacMaster P, Liu J, Shetty M, Parenteau L, Cabral C, Shields J, Blackmore S, Smith JY, Brinkman AL, Peter LE, Mathew SI, Smith KM, Borducchi EN, Rosenbloom DI, Lewis MG, Hattersley J, Li B, Hesselgesser J, Geleziunas R, Robb ML, Kim JH, Michael NL, Barouch DH (2014) Rapid seeding of the viral reservoir prior to SIV viraemia in rhesus monkeys. Nature 512:74–77PubMedPubMedCentralGoogle Scholar
  97. Williams K, Lackner A, Mallard J (2016) Non-human primate models of SIV infection and CNS neuropathology. Curr Opin Virol 19:92–98PubMedPubMedCentralGoogle Scholar
  98. Witwer KW, Gama L, Li M, Bartizal CM, Queen SE, Varrone JJ, Brice AK, Graham DR, Tarwater PM, Mankowski JL, Zink MC, Clements JE (2009) Coordinated regulation of SIV replication and immune responses in the CNS. PLoS ONE 4:e8129PubMedPubMedCentralGoogle Scholar
  99. Xu H, Wang Z, Li J, Wu H, Peng Y, Fan L, Chen J, Gu C, Yan F, Wang L, Chen G (2017) The polarization states of microglia in TBI: a new paradigm for pharmacological intervention. Neural Plast 2017:5405104PubMedPubMedCentralGoogle Scholar
  100. Yona S, Kim KW, Wolf Y, Mildner A, Varol D, Breker M, Strauss-Ayali D, Viukov S, Guilliams M, Misharin A, Hume DA, Perlman H, Malissen B, Zelzer E, Jung S (2013) Fate mapping reveals origins and dynamics of monocytes and tissue macrophages under homeostasis. Immunity 38:79–91PubMedGoogle Scholar
  101. Zayyad Z, Spudich S (2015) Neuropathogenesis of HIV: from initial neuroinvasion to HIV-associated neurocognitive disorder (HAND). Curr HIV/AIDS Rep 12:16–24PubMedPubMedCentralGoogle Scholar
  102. Zhou L, Rua R, Ng T, Vongrad V, Ho YS, Geczy C, Hsu K, Brew BJ, Saksena NK (2009) Evidence for predilection of macrophage infiltration patterns in the deeper midline and mesial temporal structures of the brain uniquely in patients with HIV-associated dementia. BMC Infect Dis 9:192PubMedPubMedCentralGoogle Scholar
  103. Zink MC, Clements JE (2002) A novel simian immunodeficiency virus model that provides insight into mechanisms of human immunodeficiency virus central nervous system disease. J Neurovirol 8(Suppl 2):42–48PubMedGoogle Scholar
  104. Zink MC, Narayan O, Kennedy PG, Clements JE (1987) Pathogenesis of visna/maedi and caprine arthritis-encephalitis: new leads on the mechanism of restricted virus replication and persistent inflammation. Vet Immunol Immunopathol 15:167–180PubMedGoogle Scholar
  105. Zink MC, Suryanarayana K, Mankowski JL, Shen A, Piatak M Jr, Spelman JP, Carter DL, Adams RJ, Lifson JD, Clements JE (1999) High viral load in the cerebrospinal fluid and brain correlates with severity of simian immunodeficiency virus encephalitis. J Virol 73:10480–10488PubMedPubMedCentralGoogle Scholar
  106. Zink MC, Brice AK, Kelly KM, Queen SE, Gama L, Li M, Adams RJ, Bartizal C, Varrone J, Rabi SA, Graham DR, Tarwater PM, Mankowski JL, Clements JE (2010) Simian immunodeficiency virus-infected macaques treated with highly active antiretroviral therapy have reduced central nervous system viral replication and inflammation but persistence of viral DNA. J Infect Dis 202:161–170PubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Lucio Gama
    • 1
  • Celina Abreu
    • 1
  • Erin N. Shirk
    • 1
  • Suzanne E. Queen
    • 1
  • Sarah E. Beck
    • 1
  • Kelly A. Metcalf Pate
    • 1
  • Brandon T. Bullock
    • 1
  • M. Christine Zink
    • 1
  • Joseph L. Mankowski
    • 1
    • 2
    • 3
  • Janice E. Clements
    • 1
    • 2
    • 3
  1. 1.Department of Molecular and Comparative PathobiologyJohns Hopkins UniversityBaltimoreUSA
  2. 2.Department of NeurologyJohns Hopkins UniversityBaltimoreUSA
  3. 3.Department of PathologyJohns Hopkins UniversityBaltimoreUSA

Personalised recommendations