Initiation of HAART during acute simian immunodeficiency virus infection rapidly controls virus replication in the CNS by enhancing immune activity and preserving protective immune responses

详细信息    查看全文

• 作者：David R. Graham (1) (2)
  Lucio Gama (1)
  Suzanne E. Queen (1)
  Ming Li (1)
  Angela K. Brice (1)
  Kathleen M. Kelly (1)
  Joseph L. Mankowski (1) (3) (4)
  Janice E. Clements (1) (3) (4) (5)
  M. Christine Zink (1) (3) (6)
  
• 关键词：SIV ; HAART ; Acute infection ; Macaque ; Immune activation ; IFN ; MxA
• 刊名：Journal of NeuroVirology
• 出版年：2011
• 出版时间：February 2011
• 年：2011
• 卷：17
• 期：1
• 页码：120-130
• 全文大小：406KB
• 参考文献：1. Ances BM, Clifford DB (2008) HIV-associated neurocognitive disorders and the impact of combination antiretroviral therapies. Curr Neurol Neurosci Rep 8:455-61 CrossRef
  2. Barber SA, Herbst DS, Bullock BT, Gama L, Clements JE (2004a) Innate immune responses and control of acute simian immunodeficiency virus replication in the central nervous system. J Neurovirol 10(Suppl 1):15-0
  3. Barber SA, Uhrlaub JL, DeWitt JB, Tarwater PM, Zink MC (2004b) Dysregulation of mitogen-activated protein kinase signaling pathways in simian immunodeficiency virus encephalitis. Am J Pathol 164:355-62 CrossRef
  4. Barber SA, Gama L, Dudaronek JM, Voelker T, Tarwater PM, Clements JE (2006) Mechanism for the establishment of transcriptional HIV latency in the brain in a simian immunodeficiency virus-macaque model. J Infect Dis 193:963-70 CrossRef
  5. Boisse L, Gill MJ, Power C (2008) HIV infection of the central nervous system: clinical features and neuropathogenesis. Neurol Clin 26:799-19, x CrossRef
  6. Clements JE, Babas T, Mankowski JL, Suryanarayana K, Piatak M Jr, Tarwater PM, Lifson JD, Zink MC (2002) 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 186:905-13 CrossRef
  7. 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 67:569-79 CrossRef
  8. 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 83:9247-257 CrossRef
  9. Dudaronek JM, Barber SA, Clements JE (2007) CUGBP1 is required for IFNbeta-mediated induction of dominant-negative CEBPbeta and suppression of SIV replication in macrophages. J Immunol 179:7262-269
  10. Heaton R, Clifford D, Woods S, Rivera Mindt M, Vigil O, Taylor M, Marcotte T, Atkinson H, Grant I (2009). HIV-associated neurocognitive impairment remains prevalent in the era of combination ART: the CHARTER study. In: 16th conference on retroviruses and opportunistic infections, Montréal, Canada
  11. 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 USA 94:8714-719 CrossRef
  12. 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 69:5337-344
  13. Henderson AJ, Connor RI, Calame KL (1996) C/EBP activators are required for HIV-1 replication and proviral induction in monocytic cell lines. Immunity 5:91-01 CrossRef
  14. 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 188:1255-265 m.188.7.1255">CrossRef
  15. Hoshino Y, Nakata K, Hoshino S, Honda Y, Tse DB, Shioda T, Rom WN, Weiden M (2002) Maximal HIV-1 replication in alveolar macrophages during tuberculosis requires both lymphocyte contact and cytokines. J Exp Med 195:495-05 m.20011614">CrossRef
  16. Kitahata MM, Gange SJ, Abraham AG, Merriman B, Saag MS, Justice AC, Hogg RS, Deeks SG, Eron JJ, Brooks JT, Rourke SB, Gill MJ, Bosch RJ, Martin JN, Klein MB, Jacobson LP, Rodriguez B, Sterling TR, Kirk GD, Napravnik S, Rachlis AR, Calzavara LM, Horberg MA, Silverberg MJ, Gebo KA, Goedert JJ, Benson CA, Collier AC, Van Rompaey SE, Crane HM, McKaig RG, Lau B, Freeman AM, Moore RD (2009) Effect of early versus deferred antiretroviral therapy for HIV on Survival. N Engl J Med 360:1815-826 CrossRef
  17. Letendre S, Marquie-Beck J, Capparelli E, Best B, Clifford D, Collier AC, Gelman BB, McArthur JC, McCutchan JA, Morgello S, Simpson D, Grant I, Ellis RJ (2008) Validation of the CNS penetration–effectiveness rank for quantifying antiretroviral penetration into the central nervous system. Arch Neurol 65:65-0 CrossRef
  18. Li H, Gade P, Xiao W, Kalvakolanu DV (2007) The interferon signaling network and transcription factor C/EBP-beta. Cell Mol Immunol 4:407-18
  19. Mankowski JL, Queen SE, Clements JE, Zink MC (2004) Cerebrospinal fluid markers that predict SIV CNS disease. J Neuroimmunol 157:66-0 m.2004.08.031">CrossRef
  20. Robertson KR, Smurzynski M, Parsons TD, Wu K, Bosch RJ, Wu J, McArthur JC, Collier AC, Evans SR, Ellis RJ (2007) The prevalence and incidence of neurocognitive impairment in the HAART era. AIDS 21:1915-921 CrossRef
  21. Schefe JH, Lehmann KE, Buschmann IR, Unger T, Funke-Kaiser H (2006) Quantitative real-time RT-PCR data analysis: current concepts and the novel “gene expression's CT difference-formula. J Mol Med 84:901-10 CrossRef
  22. Tanaka N, Hoshino Y, Gold J, Hoshino S, Martiniuk F, Kurata T, Pine R, Levy D, Rom WN, Weiden M (2005) Interleukin-10 induces inhibitory C/EBPbeta through STAT-3 and represses HIV-1 transcription in macrophages. Am J Respir Cell Mol Biol 33:406-11 mb.2005-0140OC">CrossRef
  23. 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 165:2028-039
  24. When To Start Consortium, Sterne JA, May M, Costagliola D, de Wolf F, Phillips AN, Harris R, Funk MJ, Geskus RB, Gill J, Dabis F, Miró JM, Justice AC, Ledergerber B, F?tkenheuer G, Hogg RS, Monforte AD, Saag M, Smith C, Staszewski S, Egger M, Cole SR (2009) Timing of initiation of antiretroviral therapy in AIDS-free HIV-1-infected patients: a collaborative analysis of 18 HIV cohort studies. Lancet 373:1352-363 CrossRef
  25. 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:e8129 CrossRef
  26. 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):42-8 CrossRef
  27. 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 73:10480-0488
  28. Zink MC, Coleman GD, Mankowski JL, Adams RJ, Tarwater PM, Fox K, Clements JE (2001) Increased macrophage chemoattractant protein-1 in cerebrospinal fluid precedes and predicts simian immunodeficiency virus encephalitis. J Infect Dis 184:1015-021 CrossRef
  29. Zink MC, Brice AK, Kelly KM, Queen SE, Gama L, Li M, Adams RJ, BartizalC, 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(1):161-0
  
• 作者单位：David R. Graham (1) (2)
  Lucio Gama (1)
  Suzanne E. Queen (1)
  Ming Li (1)
  Angela K. Brice (1)
  Kathleen M. Kelly (1)
  Joseph L. Mankowski (1) (3) (4)
  Janice E. Clements (1) (3) (4) (5)
  M. Christine Zink (1) (3) (6)
  
  1. Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, 733 N. Broadway, BRB 831, Baltimore, MD, 21205, USA
  2. Department of Medicine, Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA
  3. Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA
  4. Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA
  5. Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA
  6. Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, 21205, USA
  
• ISSN：1538-2443

文摘

The CNS remains vulnerable to HIV-induced damage despite highly active antiretroviral therapy (HAART). Using a rigorous simian immunodeficiency virus (SIV) macaque model of HAART that combines three classes of antiretroviral drugs (a protease inhibitor, a reverse transcriptase inhibitor, and an integrase inhibitor), we examined immune responses and virus replication in the plasma and cerebrospinal fluid (CSF) following HAART initiation during acute infection (4?days postinoculation (p.i.)). HAART-treated macaques did not experience the level of acute CD4+ and CD8+ T cell and NK cell count suppression in the peripheral blood normally observed during acute infection. Initiation of HAART produced a rapid four-log decline in viral load in plasma and a slower two-log decline of viral RNA in the CSF over the subsequent 17?days of infection. Despite a dramatic reduction of viral RNA levels in the brain at 21?days p.i., viral DNA levels were not different between the two groups. Expression of most cytokine mRNA in brain of HAART-treated macaques did not significantly differ from untreated controls. Expression of the IFN responsive gene MxA was significantly reduced in the brain of HAART-treated macaques, suggesting control of hyperactive immune responses. Control of virus replication likely was enhanced by significant increases in CD4+ and CD8+ T cell trafficking in the brain of infected animals on HAART therapy and the concomitant increase in levels of IFNγ. Collectively, these data indicate preserved innate and adaptive immune activity in the brain following HAART initiation during acute SIV infection in this macaque model, suggesting profound benefits following acute treatment of SIV.