nach oben

Erschienen in:

03.10.2017 | Review

An SIV/macaque model targeted to study HIV-associated neurocognitive disorders

verfasst von: Sarah E. Beck, Suzanne E. Queen, Kelly A. Metcalf Pate, Lisa M. Mangus, Celina M. Abreu, Lucio Gama, Kenneth W. Witwer, Robert J. Adams, M. Christine Zink, Janice E. Clements, Joseph L. Mankowski

Erschienen in: Journal of NeuroVirology | Ausgabe 2/2018

Einloggen, um Zugang zu erhalten

Abstract

Simian immunodeficiency virus (SIV) infection of pigtailed macaques is a highly representative and well-characterized animal model for HIV neuropathogenesis studies that provides an excellent opportunity to study and develop prognostic markers of HIV-associated neurocognitive disorders (HAND) for HIV-infected individuals. SIV studies can be performed in a controlled setting that enhances reproducibility and offers high-translational value. Similar to observations in HIV-infected patients receiving antiretroviral therapy (ART), ongoing neurodegeneration and inflammation are present in SIV-infected pigtailed macaques treated with suppressive ART. By developing quantitative viral outgrowth assays that measure both CD4+ T cells and macrophages harboring replication competent SIV as well as a highly sensitive mouse-based viral outgrowth assay, we have positioned the SIV/pigtailed macaque model to advance our understanding of latent cellular reservoirs, including potential CNS reservoirs, to promote HIV cure. In addition to contributing to our understanding of the pathogenesis of HAND, the SIV/pigtailed macaque model also provides an excellent opportunity to test innovative approaches to eliminate the latent HIV reservoir in the brain.

Akay C, Cooper M, Odeleye A, Jensen BK, White MG, Vassoler F et al (2014) Antiretroviral drugs induce oxidative stress and neuronal damage in the central nervous system. J Neurovirol 20(1):39–53CrossRefPubMedPubMedCentral

Antinori A, Arendt G, Becker JT, Brew BJ, Byrd DA, Cherner M et al (2007) Updated research nosology for HIV-associated neurocognitive disorders. Neurology 69(18):1789–1799CrossRefPubMedPubMedCentral

Avalos CR, Price SL, Forsyth ER, Pin JN, Shirk EN, Bullock BT et al (2016) Quantitation of productively infected monocytes and macrophages of simian immunodeficiency virus-infected macaques. J Virol 90(12):5643–5656CrossRefPubMedPubMedCentral

Beck SE, Kelly KM, Queen SE, Adams RJ, Zink MC, Tarwater PM et al (2015a) Macaque species susceptibility to simian immunodeficiency virus: increased incidence of SIV central nervous system disease in pigtailed macaques versus rhesus macaques. J Neurovirol 21(2):148–158CrossRefPubMed

Beck SE, Queen SE, Witwer KW, Metcalf Pate KA, Mangus LM, Gama L et al (2015b) Paving the path to HIV neurotherapy: predicting SIV CNS disease. Eur J Pharmacol 759:303–312CrossRefPubMedPubMedCentral

Beck SE, Queen SE, Viscidi R, Johnson D, Kent SJ, Adams RJ et al (2016) Central nervous system-specific consequences of simian immunodeficiency virus gag escape from major histocompatibility complex class I-mediated control. J Neurovirol 22(4):498–507CrossRefPubMedPubMedCentral

Brew BJ, Pemberton L, Cunningham P, Law MG (1997) Levels of human immunodeficiency virus type 1 RNA in cerebrospinal fluid correlate with AIDS dementia stage. J Infect Dis 175(4):963–966CrossRefPubMed

Charlins P, Schmitt K, Remling-Mulder L, Hogan LE, Hanhauser E, Hobbs KS et al (2017) A humanized mouse-based HIV-1 viral outgrowth assay with higher sensitivity than in vitro qVOA in detecting latently infected cells from individuals on ART with undetectable viral loads. Virology 507:135–139CrossRefPubMed

Dinoso JB, Rabi SA, Blankson JN, Gama L, Mankowski JL, Siliciano RF et al (2009) A simian immunodeficiency virus-infected macaque model to study viral reservoirs that persist during highly active antiretroviral therapy. J Virol 83(18):9247–9257CrossRefPubMedPubMedCentral

Dorsey JL, Mangus LM, Oakley JD, Beck SE, Kelly KM, Queen SE et al (2014) Loss of corneal sensory nerve fibers in SIV-infected macaques: an alternate approach to investigate HIV-induced PNS damage. Am J Pathol 184(6):1652–1659CrossRefPubMedPubMedCentral

Dorsey JL, Mangus LM, Hauer P, Ebenezer GJ, Queen SE, Laast VA, Adams RJ, Mankoski JL (2015) Persistent peripheral nervous system damage in simian immunodeficiency virus-infected macaques receiving antiretroviral therapy. J Neuropathology 74(11)

Ellis RJ, Hsia K, Spector SA, Nelson JA, Heaton RK, Wallace MR et al (1997) Cerebrospinal fluid human immunodeficiency virus type 1 RNA levels are elevated in neurocognitively impaired individuals with acquired immunodeficiency syndrome. HIV neurobehavioral research center group. Ann Neurol 42(5):679–688CrossRefPubMed

Folks TM, Justement J, Kinter A, Dinarello CA, Fauci AS (1987) Cytokine-induced expression of HIV-1 in a chronically infected promonocyte cell line. Science 238(4828):800–802CrossRefPubMed

Gama L, Abreu CM, Shirk EN, Price SL, Li M, Laird GM et al (2017) Reactivation of simian immunodeficiency virus reservoirs in the brain of virally suppressed macaques. AIDS 31(1):5–14CrossRefPubMed

Heaton RK, Clifford DB, Franklin DR Jr, Woods SP, Ake C, Vaida F et al (2010) HIV-associated neurocognitive disorders persist in the era of potent antiretroviral therapy: CHARTER study. Neurology 75(23):2087–2096CrossRefPubMedPubMedCentral

Helke KL, Queen SE, Mankowski JL (2013) 14-3-3 protein in CSF reflects SIV-mediated pre-synaptic damage. Curr HIV Res 11(4):281–287CrossRefPubMed

Ho YC, Shan L, Hosmane NN, Wang J, Laskey SB, Rosenbloom DI et al (2013) Replication-competent noninduced proviruses in the latent reservoir increase barrier to HIV-1 cure. Cell 155(3):540–551CrossRefPubMedPubMedCentral

Kelly KM, Beck SE, Metcalf Pate KA, Queen SE, Dorsey JL, Adams RJ et al (2013) Neuroprotective maraviroc monotherapy in simian immunodeficiency virus-infected macaques: reduced replicating and latent SIV in the brain. AIDS 27(18):F21–F28CrossRefPubMedPubMedCentral

Kuller LH, Tracy R, Belloso W, De Wit S, Drummond F, Lane HC et al (2008) Inflammatory and coagulation biomarkers and mortality in patients with HIV infection. PLoS Med 5(10):e203CrossRefPubMedPubMedCentral

Laast VA, Pardo CA, Tarwater PM, Queen SE, Reinhart TA, Ghosh M et al (2007) Pathogenesis of simian immunodeficiency virus-induced alterations in macaque trigeminal ganglia. J Neuropathol Exp Neurol 66(1):26–34CrossRefPubMed

Laast VA, Shim B, Johanek LM, Dorsey JL, Hauer PE, Tarwater PM et al (2011) Macrophage-mediated dorsal root ganglion damage precedes altered nerve conduction in SIV-infected macaques. Am J Pathol 179(5):2337–2345CrossRefPubMedPubMedCentral

Levine AJ, Service S, Miller EN, Reynolds SM, Singer EJ, Shapshak P et al (2012) Genome-wide association study of neurocognitive impairment and dementia in HIV-infected adults. Am J Med Genet B Neuropsychiatr Genet 159B(6):669–683CrossRefPubMedPubMedCentral

Mangus LM, Dorsey JL, Laast VA, Hauer P, Queen SE, Adams RJ et al (2015) Neuroinflammation and virus replication in the spinal cord of simian immunodeficiency virus-infected macaques. J Neuropathol Exp Neurol 74(1):38–47CrossRefPubMedPubMedCentral

Mankowski JL, Flaherty MT, Spelman JP, Hauer DA, Didier PJ, Amedee AM et al (1997) Pathogenesis of simian immunodeficiency virus encephalitis: viral determinants of neurovirulence. J Virol 71(8):6055–6060PubMedPubMedCentral

Mankowski JL, Queen SE, Kirstein LM, Spelman JP, Laterra J, Simpson IA et al (1999) Alterations in blood-brain barrier glucose transport in SIV-infected macaques. J Neurovirol 5(6):695–702CrossRefPubMed

Mankowski JL, Clements JE, Zink MC (2002a) Searching for clues: tracking the pathogenesis of human immunodeficiency virus central nervous system disease by use of an accelerated, consistent simian immunodeficiency virus macaque model. J Infect Dis 186(Suppl 2):S199–S208CrossRefPubMed

Mankowski JL, Queen SE, Tarwater PM, Fox KJ, Perry VH (2002b) Accumulation of beta-amyloid precursor protein in axons correlates with CNS expression of SIV gp41. J Neuropathol Exp Neurol 61(1):85–90CrossRefPubMed

Mankowski JL, Queen SE, Tarwater PJ, Adams RJ, Guilarte TR (2003) Elevated peripheral benzodiazepine receptor expression in simian immunodeficiency virus encephalitis. J Neurovirol 9(1):94–100CrossRefPubMed

Mankowski JL, Queen SE, Clements JE, Zink MC (2004) Cerebrospinal fluid markers that predict SIV CNS disease. J Neuroimmunol 157(1–2):66–70CrossRefPubMed

Mankowski JL, Queen SE, Fernandez CS, Tarwater PM, Karper JM, Adams RJ et al (2008) Natural host genetic resistance to lentiviral CNS disease: a neuroprotective MHC class I allele in SIV-infected macaques. PLoS One 3(11):e3603CrossRefPubMedPubMedCentral

McArthur JC, McClernon DR, Cronin MF, Nance-Sproson TE, Saah AJ, St Clair M et al (1997) Relationship between human immunodeficiency virus-associated dementia and viral load in cerebrospinal fluid and brain. Ann Neurol 42(5):689–698CrossRefPubMed

McGovern N, Schlitzer A, Gunawan M, Jardine L, Shin A, Poyner E et al (2014) Human dermal CD14(+) cells are a transient population of monocyte-derived macrophages. Immunity 41(3):465–477CrossRefPubMedPubMedCentral

Metcalf Pate KA, Lyons CE, Dorsey JL, Shirk EN, Queen SE, Adams RJ et al (2013) Platelet activation and platelet-monocyte aggregate formation contribute to decreased platelet count during acute simian immunodeficiency virus infection in pig-tailed macaques. J Infect Dis 208(6):874–883CrossRefPubMedPubMedCentral

Metcalf Pate KA, Pohlmeyer CW, Walker-Sperling VE, Foote JB, Najarro KM, Cryer CG et al (2015) A murine viral outgrowth assay to detect residual HIV type 1 in patients with undetectable viral loads. J Infect Dis 212(9):1387–1396CrossRefPubMedPubMedCentral

Meulendyke KA, Queen SE, Engle EL, Shirk EN, Liu J, Steiner JP et al (2014) Combination fluconazole/paroxetine treatment is neuroprotective despite ongoing neuroinflammation and viral replication in an SIV model of HIV neurological disease. J Neurovirol 20(6):591–602CrossRefPubMedPubMedCentral

Mothobi NZ, Brew BJ (2012) Neurocognitive dysfunction in the highly active antiretroviral therapy era. Curr Opin Infect Dis 25(1):4–9CrossRefPubMed

Mudd JC, Panigrahi S, Kyi B, Moon SH, Manion MM, Younes SA et al (2016) Inflammatory function of CX3CR1+ CD8+ T cells in treated HIV infection is modulated by platelet interactions. J Infect Dis 214(12):1808–1816CrossRefPubMedPubMedCentral

Queen SE, Mears BM, Kelly KM, Dorsey JL, Liao Z, Dinoso JB et al (2011) Replication-competent simian immunodeficiency virus (SIV) gag escape mutations archived in latent reservoirs during antiretroviral treatment of SIV-infected macaques. J Virol 85(17):9167–9175CrossRefPubMedPubMedCentral

Ratai EM, Pilkenton S, He J, Fell R, Bombardier JP, Joo CG et al (2011) CD8+ lymphocyte depletion without SIV infection does not produce metabolic changes or pathological abnormalities in the rhesus macaque brain. J Med Primatol 40(5):300–309CrossRefPubMedPubMedCentral

Ravimohan S, Gama L, Engle EL, Zink MC, Clements JE (2012) Early emergence and selection of a SIV-LTR C/EBP site variant in SIV-infected macaques that increases virus infectivity. PLoS One 7(8):e42801CrossRefPubMedPubMedCentral

Saylor D, Dickens AM, Sacktor N, Haughey N, Slusher B, Pletnikov M et al (2016) HIV-associated neurocognitive disorder—pathogenesis and prospects for treatment. Nat Rev Neurol 12(4):234–248CrossRefPubMedPubMedCentral

Schmitz JE, Kuroda MJ, Santra S, Sasseville VG, Simon MA, Lifton MA et al (1999) Control of viremia in simian immunodeficiency virus infection by CD8+ lymphocytes. Science 283(5403):857–860CrossRefPubMed

Shen A, Zink MC, Mankowski JL, Chadwick K, Margolick JB, Carruth LM et al (2003) Resting CD4+ T lymphocytes but not thymocytes provide a latent viral reservoir in a simian immunodeficiency virus-Macaca nemestrina model of human immunodeficiency virus type 1-infected patients on highly active antiretroviral therapy. J Virol 77(8):4938–4949CrossRefPubMedPubMedCentral

Shen A, Yang HC, Zhou Y, Chase AJ, Boyer JD, Zhang H et al (2007) Novel pathway for induction of latent virus from resting CD4(+) T cells in the simian immunodeficiency virus/macaque model of human immunodeficiency virus type 1 latency. J Virol 81(4):1660–1670CrossRefPubMed

Singh MV, Davidson DC, Jackson JW, Singh VB, Silva J, Ramirez SH et al (2014) Characterization of platelet-monocyte complexes in HIV-1-infected individuals: possible role in HIV-associated neuroinflammation. J Immunol 192(10):4674–4684CrossRefPubMedPubMedCentral

Smith MZ, Dale CJ, De Rose R, Stratov I, Fernandez CS, Brooks AG et al (2005a) Analysis of pigtail macaque major histocompatibility complex class I molecules presenting immunodominant simian immunodeficiency virus epitopes. J Virol 79(2):684–695CrossRefPubMedPubMedCentral

Smith MZ, Fernandez CS, Chung A, Dale CJ, De Rose R, Lin J et al (2005b) The pigtail macaque MHC class I allele mane-a*10 presents an immundominant SIV gag epitope: identification, tetramer development and implications of immune escape and reversion. J Med Primatol 34(5–6):282–293CrossRefPubMed

Swirski FK, Nahrendorf M, Etzrodt M, Wildgruber M, Cortez-Retamozo V, Panizzi P et al (2009) Identification of splenic reservoir monocytes and their deployment to inflammatory sites. Science 325(5940):612–616CrossRefPubMedPubMedCentral

Thompson KA, Kent SJ, Gahan ME, Purcell DF, McLean CA, Preiss S et al (2003) Decreased neurotropism of nef long terminal repeat (nef/LTR)-deleted simian immunodeficiency virus. J Neurovirol 9(4):442–451CrossRefPubMed

van der Laan AM, Ter Horst EN, Delewi R, Begieneman MP, Krijnen PA, Hirsch A et al (2014) Monocyte subset accumulation in the human heart following acute myocardial infarction and the role of the spleen as monocyte reservoir. Eur Heart J 35(6):376–385CrossRefPubMed

Wachtman LM, Tarwater PM, Queen SE, Adams RJ, Mankowski JL (2006) Platelet decline: an early predictive hematologic marker of simian immunodeficiency virus central nervous system disease. J Neurovirol 12(1):25–33CrossRefPubMed

Wachtman LM, Skolasky RL, Tarwater PM, Esposito D, Schifitto G, Marder K et al (2007) Platelet decline: an avenue for investigation into the pathogenesis of human immunodeficiency virus-associated dementia. Arch Neurol 64(9):1264–1272CrossRefPubMed

Weed MR, Hienz RD, Brady JV, Adams RJ, Mankowski JL, Clements JE et al (2003) Central nervous system correlates of behavioral deficits following simian immunodeficiency virus infection. J Neurovirol 9(4):452–464CrossRefPubMed

Whitney JB, Hill AL, Sanisetty S, Penaloza-MacMaster P, Liu J, Shetty M et al (2014) Rapid seeding of the viral reservoir prior to SIV viraemia in rhesus monkeys. Nature 512(7512):74–77CrossRefPubMedPubMedCentral

Williams K, Burdo TH (2012) Monocyte mobilization, activation markers, and unique macrophage populations in the brain: observations from SIV infected monkeys are informative with regard to pathogenic mechanisms of HIV infection in humans. J Neuroimmune Pharmacol 7(2):363–371CrossRefPubMed

Yuan Z, Kang G, Lu W, Li Q (2017) Reactivation of HIV-1 proviruses in immune-compromised mice engrafted with human VOA-negative CD4+ T cells. J Virus Erad 3(1):61–65PubMedPubMedCentral

Zink MC, Suryanarayana K, Mankowski JL, Shen A, Piatak M Jr, Spelman JP et al (1999) High viral load in the cerebrospinal fluid and brain correlates with severity of simian immunodeficiency virus encephalitis. J Virol 73(12):10480–10488PubMedPubMedCentral

Zink MC, Uhrlaub J, DeWitt J, Voelker T, Bullock B, Mankowski J et al (2005) Neuroprotective and anti-human immunodeficiency virus activity of minocycline. JAMA 293(16):2003–2011CrossRefPubMed

Zink MC, Brice AK, Kelly KM, Queen SE, Gama L, Li M et al (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):161–170CrossRefPubMedPubMedCentral

Titel: An SIV/macaque model targeted to study HIV-associated neurocognitive disorders
verfasst von: Sarah E. Beck
Suzanne E. Queen
Kelly A. Metcalf Pate
Lisa M. Mangus
Celina M. Abreu
Lucio Gama
Kenneth W. Witwer
Robert J. Adams
M. Christine Zink
Janice E. Clements
Joseph L. Mankowski
Publikationsdatum: 03.10.2017
Verlag: Springer International Publishing
Erschienen in: Journal of NeuroVirology / Ausgabe 2/2018
Print ISSN: 1355-0284
Elektronische ISSN: 1538-2443
DOI: https://doi.org/10.1007/s13365-017-0582-4

Leitlinien kompakt für die Neurologie

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Neurologie

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Frühe Alzheimertherapie lohnt sich

25.04.2024 AAN-Jahrestagung 2024 Nachrichten

Ist die Tau-Last noch gering, scheint der Vorteil von Lecanemab besonders groß zu sein. Und beginnen Erkrankte verzögert mit der Behandlung, erreichen sie nicht mehr die kognitive Leistung wie bei einem früheren Start. Darauf deuten neue Analysen der Phase-3-Studie Clarity AD.

Viel Bewegung in der Parkinsonforschung

25.04.2024 Parkinson-Krankheit Nachrichten

Neue arznei- und zellbasierte Ansätze, Frühdiagnose mit Bewegungssensoren, Rückenmarkstimulation gegen Gehblockaden – in der Parkinsonforschung tut sich einiges. Auf dem Deutschen Parkinsonkongress ging es auch viel um technische Innovationen.

Demenzkranke durch Antipsychotika vielfach gefährdet

23.04.2024 Demenz Nachrichten

Wenn Demenzkranke aufgrund von Symptomen wie Agitation oder Aggressivität mit Antipsychotika behandelt werden, sind damit offenbar noch mehr Risiken verbunden als bislang angenommen.

Update Neurologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 2/2018

Humanized mice: models for evaluating NeuroHIV and cure strategies

An SIV macaque model of SIV and HAND: the need for adjunctive therapies in HIV that target activated monocytes and macrophages

Doxycycline-inducible and astrocyte-specific HIV-1 Tat transgenic mice (iTat) as an HIV/neuroAIDS model

Evolution of the HIV-1 transgenic rat: utility in assessing the progression of HIV-1-associated neurocognitive disorders

Changing clinical phenotypes of HIV-associated neurocognitive disorders