Skip to main content
SpringerLink
Log in

Inflammatory Mechanisms and Cascades Contributing to Neurocognitive Impairment in HIV/AIDS

  • Chapter
  • First Online:
Neurocognitive Complications of HIV-Infection

Part of the book series: Current Topics in Behavioral Neurosciences ((CTBN,volume 50))

Abstract

Neurocognitive impairment caused by chronic human immunodeficiency virus (HIV) infection is a growing concern. In this chapter we discuss the inflammatory mechanisms underlying the pathology of asymptomatic and mild neurocognitive impairment in the context of antiretroviral therapy. We discuss the role of HIV, viral proteins, and virally infected cells on the development of neuroinflammation and the effect of viral proteins on the cells of the central nervous system.

We examine how these collective factors result in an inflammatory context that triggers the development of neurocognitive impairment in HIV. We assess the contribution of antiretrovirals and drugs of abuse, including methamphetamine, cannabis, and opioids, to the neurotoxic and neuroinflammatory milieu that leads to the development of neurocognitive impairment in HIV-infected individuals. We also examined circulating biomarkers, NF-L, sCD163, and sCD14, pertinent to identifying changes in the CNS that could indicate real-time changes in patient physiology. Lastly, we discuss future studies, such as exosomes and the microbiome, which could play a role in the HIV-induced neuroinflammation that eventually manifests as cognitive impairment.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 119.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 159.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Abdulle S, Mellgren A, Brew BJ, Cinque P, Hagberg L, Price RW et al (2007) CSF neurofilament protein (NFL) – a marker of active HIV-related neurodegeneration. J Neurol 254(8):1026–1032

    CAS  PubMed  Google Scholar 

  • Allam O, Samarani S, Mehraj V, Jenabian MA, Tremblay C, Routy JP et al (2018) HIV induces production of IL-18 from intestinal epithelial cells that increases intestinal permeability and microbial translocation. PLoS One 13(3):e0194185

    PubMed  PubMed Central  Google Scholar 

  • Alvarez-Erviti L, Seow Y, Yin H, Betts C, Lakhal S, Wood MJ (2011) Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. Nat Biotechnol 29(4):341–345

    CAS  PubMed  Google Scholar 

  • Ancuta P, Kamat A, Kunstman KJ, Kim EY, Autissier P, Wurcel A et al (2008) Microbial translocation is associated with increased monocyte activation and dementia in AIDS patients. PLoS One 3(6):e2516

    PubMed  PubMed Central  Google Scholar 

  • Aweeka F, Jayewardene A, Staprans S, Bellibas SE, Kearney B, Lizak P et al (1999) Failure to detect nelfinavir in the cerebrospinal fluid of HIV-1-infected patients with and without AIDS dementia complex. J Acquir Immune Defic Syndr Hum Retrovirol 20(1):39–43

    CAS  PubMed  Google Scholar 

  • Baxter AE, Russell RA, Duncan CJ, Moore MD, Willberg CB, Pablos JL et al (2014) Macrophage infection via selective capture of HIV-1-infected CD4+ T cells. Cell Host Microbe 16(6):711–721

    CAS  PubMed  PubMed Central  Google Scholar 

  • Beltran LM, Munoz Hernandez R, de Pablo Bernal RS, Garcia Morillo JS, Egido J, Noval ML et al (2014) Reduced sTWEAK and increased sCD163 levels in HIV-infected patients: modulation by antiretroviral treatment, HIV replication and HCV co-infection. PLoS One 9(3):e90541

    PubMed  PubMed Central  Google Scholar 

  • Brenchley JM, Douek DC (2008) HIV infection and the gastrointestinal immune system. Mucosal Immunol 1(1):23–30

    CAS  PubMed  PubMed Central  Google Scholar 

  • Bryant AK, Moore DJ, Burdo TH, Lakritz JR, Gouaux B, Soontornniyomkij V et al (2017) Plasma soluble CD163 is associated with postmortem brain pathology in human immunodeficiency virus infection. AIDS 31(7):973–979

    CAS  PubMed  Google Scholar 

  • Burdo TH, Weiffenbach A, Woods SP, Letendre S, Ellis RJ, Williams KC (2013) Elevated sCD163 in plasma but not cerebrospinal fluid is a marker of neurocognitive impairment in HIV infection. AIDS 27(9):1387–1395

    CAS  PubMed  Google Scholar 

  • Byrd DA, Fellows RP, Morgello S, Franklin D, Heaton RK, Deutsch R et al (2011) Neurocognitive impact of substance use in HIV infection. J Acquir Immune Defic Syndr 58(2):154–162

    PubMed  PubMed Central  Google Scholar 

  • Cabral GA, Griffin-Thomas L (2009) Emerging role of the cannabinoid receptor CB2 in immune regulation: therapeutic prospects for neuroinflammation. Expert Rev Mol Med 11:e3

    PubMed  PubMed Central  Google Scholar 

  • Cahill CM, Taylor AM (2017) Neuroinflammation-a co-occurring phenomenon linking chronic pain and opioid dependence. Curr Opin Behav Sci 13:171–177

    PubMed  PubMed Central  Google Scholar 

  • Castley A, Williams L, James I, Guelfi G, Berry C, Nolan D (2016) Plasma CXCL10, sCD163 and sCD14 levels have distinct associations with antiretroviral treatment and cardiovascular disease risk factors. PLoS One 11(6):e0158169

    PubMed  PubMed Central  Google Scholar 

  • Ceccarelli G, Fratino M, Selvaggi C, Giustini N, Serafino S, Schietroma I et al (2017) A pilot study on the effects of probiotic supplementation on neuropsychological performance and microRNA-29a-c levels in antiretroviral-treated HIV-1-infected patients. Brain Behav 7(8):e00756

    PubMed  PubMed Central  Google Scholar 

  • Cenker JJ, Stultz RD, McDonald D (2017) Brain microglial cells are highly susceptible to HIV-1 infection and spread. AIDS Res Hum Retroviruses 33(11):1155–1165

    CAS  PubMed  PubMed Central  Google Scholar 

  • Chan P, Hellmuth J, Colby D, Kroon E, Sacdalan C, Fletcher J et al (2018) Safety of lumbar puncture procedure in an international research setting during acute HIV infection. J Virus Erad 4(1):16–20

    PubMed  PubMed Central  Google Scholar 

  • Chen NC, Partridge AT, Sell C, Torres C, Martin-Garcia J (2017) Fate of microglia during HIV-1 infection: from activation to senescence? Glia 65(3):431–446

    PubMed  Google Scholar 

  • Chompre G, Cruz E, Maldonado L, Rivera-Amill V, Porter JT, Noel RJ Jr (2013) Astrocytic expression of HIV-1 Nef impairs spatial and recognition memory. Neurobiol Dis 49:128–136

    CAS  PubMed  Google Scholar 

  • Churchill MJ, Wesselingh SL, Cowley D, Pardo CA, McArthur JC, Brew BJ et al (2009) Extensive astrocyte infection is prominent in human immunodeficiency virus-associated dementia. Ann Neurol 66(2):253–258

    PubMed  Google Scholar 

  • Clayton KL, Garcia JV, Clements JE, Walker BD (2017) HIV infection of macrophages: implications for pathogenesis and cure. Pathog Immun 2(2):179–192

    PubMed  PubMed Central  Google Scholar 

  • Dalvi P, Sun B, Tang N, Pulliam L (2017) Immune activated monocyte exosomes alter microRNAs in brain endothelial cells and initiate an inflammatory response through the TLR4/MyD88 pathway. Sci Rep 7(1):9954

    PubMed  PubMed Central  Google Scholar 

  • Dalwadi DA, Kim S, Amdani SM, Chen Z, Huang RQ, Schetz JA (2016) Molecular mechanisms of serotonergic action of the HIV-1 antiretroviral efavirenz. Pharmacol Res 110:10–24

    CAS  PubMed  PubMed Central  Google Scholar 

  • Dillon SM, Frank DN, Wilson CC (2016) The gut microbiome and HIV-1 pathogenesis: a two-way street. AIDS 30(18):2737–2751

    CAS  PubMed  Google Scholar 

  • Dominguez-Bello MG, Costello EK, Contreras M, Magris M, Hidalgo G, Fierer N et al (2010) Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns. Proc Natl Acad Sci U S A 107(26):11971–11975

    PubMed  PubMed Central  Google Scholar 

  • Dubovy P, Klusakova I, Hradilova-Svizenska I, Joukal M, Boadas-Vaello P (2018) Activation of astrocytes and microglial cells and CCL2/CCR2 upregulation in the dorsolateral and ventrolateral nuclei of periaqueductal gray and rostral ventromedial medulla following different types of sciatic nerve injury. Front Cell Neurosci 12:40

    PubMed  PubMed Central  Google Scholar 

  • Ellery PJ, Tippett E, Chiu YL, Paukovics G, Cameron PU, Solomon A et al (2007) The CD16+ monocyte subset is more permissive to infection and preferentially harbors HIV-1 in vivo. J Immunol 178(10):6581–6589

    CAS  PubMed  Google Scholar 

  • Etzerodt A, Rasmussen MR, Svendsen P, Chalaris A, Schwarz J, Galea I et al (2014) Structural basis for inflammation-driven shedding of CD163 ectodomain and tumor necrosis factor-alpha in macrophages. J Biol Chem 289(2):778–788

    CAS  PubMed  Google Scholar 

  • Eugenin EA, King JE, Nath A, Calderon TM, Zukin RS, Bennett MV et al (2007) HIV-tat induces formation of an LRP-PSD-95- NMDAR-nNOS complex that promotes apoptosis in neurons and astrocytes. Proc Natl Acad Sci U S A 104(9):3438–3443

    CAS  PubMed  PubMed Central  Google Scholar 

  • Eugenin EA, Clements JE, Zink MC, Berman JW (2011) Human immunodeficiency virus infection of human astrocytes disrupts blood-brain barrier integrity by a gap junction-dependent mechanism. J Neurosci 31(26):9456–9465

    CAS  PubMed  PubMed Central  Google Scholar 

  • Fabbiani M, Muscatello A, Perseghin P, Bani M, Incontri A, Squillace N et al (2017) Brief report: peripheral monocyte/macrophage phenotypes associated with the evolution of cognitive performance in HIV-infected patients. J Acquir Immune Defic Syndr 76(2):219–224

    CAS  PubMed  Google Scholar 

  • Fabriek BO, van Bruggen R, Deng DM, Ligtenberg AJ, Nazmi K, Schornagel K et al (2009) The macrophage scavenger receptor CD163 functions as an innate immune sensor for bacteria. Blood 113(4):887–892

    CAS  PubMed  Google Scholar 

  • Fischer-Smith T, Bell C, Croul S, Lewis M, Rappaport J (2008) Monocyte/macrophage trafficking in acquired immunodeficiency syndrome encephalitis: lessons from human and nonhuman primate studies. J Neurovirol 14(4):318–326

    CAS  PubMed  PubMed Central  Google Scholar 

  • Gareau MG (2016) Cognitive function and the microbiome. Int Rev Neurobiol 131:227–246

    CAS  PubMed  Google Scholar 

  • Gatch MB, Kozlenkov A, Huang RQ, Yang W, Nguyen JD, Gonzalez-Maeso J et al (2013) The HIV antiretroviral drug efavirenz has LSD-like properties. Neuropsychopharmacology 38(12):2373–2384

    CAS  PubMed  PubMed Central  Google Scholar 

  • Gelman BB, Lisinicchia JG, Chen T, Johnson KM, Jennings K, Freeman DH Jr et al (2012) Prefrontal dopaminergic and enkephalinergic synaptic accommodation in HIV-associated neurocognitive disorders and encephalitis. J Neuroimmune Pharmacol 7(3):686–700

    PubMed  PubMed Central  Google Scholar 

  • Giau VV, Wu SY, Jamerlan A, An SSA, Kim SY, Hulme J (2018) Gut microbiota and their neuroinflammatory implications in Alzheimer’s disease. Nutrients 10(11). pii: E1765

    Google Scholar 

  • Gill AJ, Kovacsics CE, Cross SA, Vance PJ, Kolson LL, Jordan-Sciutto KL et al (2014) Heme oxygenase-1 deficiency accompanies neuropathogenesis of HIV-associated neurocognitive disorders. J Clin Invest 124(10):4459–4472

    PubMed  PubMed Central  Google Scholar 

  • Ginsberg SD, Alldred MJ, Gunnam SM, Schiroli C, Lee SH, Morgello S et al (2018) Expression profiling suggests microglial impairment in human immunodeficiency virus neuropathogenesis. Ann Neurol 83(2):406–417

    CAS  PubMed  PubMed Central  Google Scholar 

  • Gisslen M, Price RW, Andreasson U, Norgren N, Nilsson S, Hagberg L et al (2016) Plasma concentration of the neurofilament light protein (NFL) is a biomarker of CNS injury in HIV infection: a cross-sectional study. EBioMedicine 3:135–140

    PubMed  Google Scholar 

  • Goetzl EJ, Boxer A, Schwartz JB, Abner EL, Petersen RC, Miller BL et al (2015) Altered lysosomal proteins in neural-derived plasma exosomes in preclinical Alzheimer disease. Neurology 85(1):40–47

    CAS  PubMed  PubMed Central  Google Scholar 

  • Goetzl EJ, Goetzl L, Karliner JS, Tang N, Pulliam L (2016) Human plasma platelet-derived exosomes: effects of aspirin. FASEB J 30(5):2058–2063

    CAS  PubMed  PubMed Central  Google Scholar 

  • Goetzl EJ, Abner EL, Jicha GA, Kapogiannis D, Schwartz JB (2018a) Declining levels of functionally specialized synaptic proteins in plasma neuronal exosomes with progression of Alzheimer’s disease. FASEB J 32(2):888–893

    CAS  PubMed  Google Scholar 

  • Goetzl EJ, Schwartz JB, Abner EL, Jicha GA, Kapogiannis D (2018b) High complement levels in astrocyte-derived exosomes of Alzheimer disease. Ann Neurol 83(3):544–552

    CAS  PubMed  PubMed Central  Google Scholar 

  • Goetzl EJ, Elahi FM, Mustapic M, Kapogiannis D, Pryhoda M, Gilmore A et al (2019) Altered levels of plasma neuron-derived exosomes and their cargo proteins characterize acute and chronic mild traumatic brain injury. FASEB J 33(4):5082–5088. https://doi.org/10.1096/fj.201802319R

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Guo L, Xing Y, Pan R, Jiang M, Gong Z, Lin L et al (2013) Curcumin protects microglia and primary rat cortical neurons against HIV-1 gp120-mediated inflammation and apoptosis. PLoS One 8(8):e70565

    CAS  PubMed  PubMed Central  Google Scholar 

  • Gupta A, Pulliam L (2014) Exosomes as mediators of neuroinflammation. J Neuroinflammation 11:68

    PubMed  PubMed Central  Google Scholar 

  • He J, Chen Y, Farzan M, Choe H, Ohagen A, Gartner S et al (1997) CCR3 and CCR5 are co-receptors for HIV-1 infection of microglia. Nature 385(6617):645–649

    CAS  PubMed  Google Scholar 

  • 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):2087–2096

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hellmuth J, Valcour V, Spudich S (2015) CNS reservoirs for HIV: implications for eradication. J Virus Erad 1(2):67–71

    PubMed  PubMed Central  Google Scholar 

  • Hileman CO, Funderburg NT (2017) Inflammation, immune activation, and antiretroviral therapy in HIV. Curr HIV/AIDS Rep 14(3):93–100

    PubMed  PubMed Central  Google Scholar 

  • Hogger P, Sorg C (2001) Soluble CD163 inhibits phorbol ester-induced lymphocyte proliferation. Biochem Biophys Res Commun 288(4):841–843

    CAS  PubMed  Google Scholar 

  • Hunt PW (2016) Soluble CD163 and clinical outcomes in treated HIV infection: insights into mechanisms. J Infect Dis 214(8):1132–1133

    PubMed  Google Scholar 

  • Imp BM, Rubin LH, Tien PC, Plankey MW, Golub ET, French AL et al (2017) Monocyte activation is associated with worse cognitive performance in HIV-infected women with virologic suppression. J Infect Dis 215(1):114–121

    CAS  PubMed  Google Scholar 

  • Ismail N, Wang Y, Dakhlallah D, Moldovan L, Agarwal K, Batte K et al (2013) Macrophage microvesicles induce macrophage differentiation and miR-223 transfer. Blood 121(6):984–995

    CAS  PubMed  PubMed Central  Google Scholar 

  • Jakubzick CV, Randolph GJ, Henson PM (2017) Monocyte differentiation and antigen-presenting functions. Nat Rev Immunol 17(6):349–362

    CAS  PubMed  Google Scholar 

  • Jaureguiberry-Bravo M, Wilson R, Carvallo L, Berman JW (2016) Opioids and opioid maintenance therapies: their impact on monocyte-mediated HIV neuropathogenesis. Curr HIV Res 14(5):417–430

    CAS  PubMed  PubMed Central  Google Scholar 

  • Jessen Krut J, Mellberg T, Price RW, Hagberg L, Fuchs D, Rosengren L et al (2014) Biomarker evidence of axonal injury in neuroasymptomatic HIV-1 patients. PLoS One 9(2):e88591

    PubMed  PubMed Central  Google Scholar 

  • Kahouadji Y, Dumurgier J, Sellier P, Lapalus P, Delcey V, Bergmann J et al (2013) Cognitive function after several years of antiretroviral therapy with stable central nervous system penetration score. HIV Med 14(5):311–315

    CAS  PubMed  Google Scholar 

  • Kamat A, Lyons JL, Misra V, Uno H, Morgello S, Singer EJ et al (2012) Monocyte activation markers in cerebrospinal fluid associated with impaired neurocognitive testing in advanced HIV infection. J Acquir Immune Defic Syndr 60(3):234–243

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kanmogne GD (2005) Noninfectious pulmonary complications of HIV/AIDS. Curr Opin Pulm Med 11(3):208–212

    PubMed  Google Scholar 

  • Kanmogne GD, Schall K, Leibhart J, Knipe B, Gendelman HE, Persidsky Y (2007) HIV-1 gp120 compromises blood-brain barrier integrity and enhances monocyte migration across blood-brain barrier: implication for viral neuropathogenesis. J Cereb Blood Flow Metab 27(1):123–134

    CAS  PubMed  Google Scholar 

  • Kesby JP, Najera JA, Romoli B, Fang Y, Basova L, Birmingham A et al (2017) HIV-1 TAT protein enhances sensitization to methamphetamine by affecting dopaminergic function. Brain Behav Immun 65:210–221

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kitayama H, Miura Y, Ando Y, Hoshino S, Ishizaka Y, Koyanagi Y (2008) Human immunodeficiency virus type 1 Vpr inhibits axonal outgrowth through induction of mitochondrial dysfunction. J Virol 82(5):2528–2542

    CAS  PubMed  Google Scholar 

  • Knudsen TB, Ertner G, Petersen J, Moller HJ, Moestrup SK, Eugen-Olsen J et al (2016) Plasma soluble CD163 level independently predicts all-cause mortality in HIV-1-infected individuals. J Infect Dis 214(8):1198–1204

    CAS  PubMed  Google Scholar 

  • Koay WLA, Siems LV, Persaud D (2018) The microbiome and HIV persistence: implications for viral remission and cure. Curr Opin HIV AIDS 13(1):61–68

    CAS  PubMed  PubMed Central  Google Scholar 

  • Koneru R, Bimonte-Nelson H, Ciavatta V, Haile W, Elmore K, Ward J et al (2018) Reversing interferon-alpha neurotoxicity in a HIV-associated neurocognitive disorder mouse model. AIDS 32(11):1403–1411

    CAS  PubMed  Google Scholar 

  • Kovalevich J, Langford D (2012) Neuronal toxicity in HIV CNS disease. Future Virol 7(7):687–698

    CAS  PubMed  PubMed Central  Google Scholar 

  • Letendre SL, McCutchan JA, Childers ME, Woods SP, Lazzaretto D, Heaton RK et al (2004) Enhancing antiretroviral therapy for human immunodeficiency virus cognitive disorders. Ann Neurol 56(3):416–423

    PubMed  Google Scholar 

  • Liang H, Duan Z, Li D, Li D, Wang Z, Ren L et al (2015) Higher levels of circulating monocyte-platelet aggregates are correlated with viremia and increased sCD163 levels in HIV-1 infection. Cell Mol Immunol 12(4):435–443

    CAS  PubMed  Google Scholar 

  • Liu Y, Liu H, Kim BO, Gattone VH, Li J, Nath A et al (2004) CD4-independent infection of astrocytes by human immunodeficiency virus type 1: requirement for the human mannose receptor. J Virol 78(8):4120–4133

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lopez-Cortes LF, Trujillo-Rodriguez M, Baez-Palomo A, Benmarzouk-Hidalgo OJ, Dominguez-Molina B, Milanes-Guisado Y et al (2018) Eradication of hepatitis C virus (HCV) reduces immune activation, microbial translocation, and the HIV DNA level in HIV/HCV-coinfected patients. J Infect Dis 218(4):624–632

    CAS  PubMed  Google Scholar 

  • Lyons JL, Uno H, Ancuta P, Kamat A, Moore DJ, Singer EJ et al (2011) Plasma sCD14 is a biomarker associated with impaired neurocognitive test performance in attention and learning domains in HIV infection. J Acquir Immune Defic Syndr 57(5):371–379

    CAS  PubMed  PubMed Central  Google Scholar 

  • Marchetti G, Tincati C, Silvestri G (2013) Microbial translocation in the pathogenesis of HIV infection and AIDS. Clin Microbiol Rev 26(1):2–18

    CAS  PubMed  PubMed Central  Google Scholar 

  • Marra CM, Zhao Y, Clifford DB, Letendre S, Evans S, Henry K et al (2009) Impact of combination antiretroviral therapy on cerebrospinal fluid HIV RNA and neurocognitive performance. AIDS 23(11):1359–1366

    PubMed  Google Scholar 

  • Martin CR, Osadchiy V, Kalani A, Mayer EA (2018) The brain-gut-microbiome axis. Cell Mol Gastroenterol Hepatol 6(2):133–148

    PubMed  PubMed Central  Google Scholar 

  • McGuire JL, Gill AJ, Douglas SD, Kolson DL, CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) Group (2015) Central and peripheral markers of neurodegeneration and monocyte activation in HIV-associated neurocognitive disorders. J Neurovirol 21(4):439–448

    CAS  PubMed  PubMed Central  Google Scholar 

  • Mediouni S, Darque A, Baillat G, Ravaux I, Dhiver C, Tissot-Dupont H et al (2012) Antiretroviral therapy does not block the secretion of the human immunodeficiency virus tat protein. Infect Disord Drug Targets 12(1):81–86

    CAS  PubMed  Google Scholar 

  • Mediouni S, Marcondes MC, Miller C, McLaughlin JP, Valente ST (2015) The cross-talk of HIV-1 Tat and methamphetamine in HIV-associated neurocognitive disorders. Front Microbiol 6:1164

    PubMed  PubMed Central  Google Scholar 

  • Mellgren A, Price RW, Hagberg L, Rosengren L, Brew BJ, Gisslen M (2007) Antiretroviral treatment reduces increased CSF neurofilament protein (NFL) in HIV-1 infection. Neurology 69(15):1536–1541

    CAS  PubMed  Google Scholar 

  • Michel L, Prat A (2016) One more role for the gut: microbiota and blood brain barrier. Ann Transl Med 4(1):15

    PubMed  PubMed Central  Google Scholar 

  • Milloy MJ, Marshall B, Kerr T, Richardson L, Hogg R, Guillemi S et al (2015) High-intensity cannabis use associated with lower plasma human immunodeficiency virus-1 RNA viral load among recently infected people who use injection drugs. Drug Alcohol Rev 34(2):135–140

    PubMed  Google Scholar 

  • Nair M, Maria JM, Agudelo M, Yndart A, Vargas-Rivera ME (2015) Platelets contribute to BBB disruption induced by HIV and alcohol. J Alcohol Drug Depend 3(1):182

    PubMed  PubMed Central  Google Scholar 

  • Nedellec R, Coetzer M, Shimizu N, Hoshino H, Polonis VR, Morris L et al (2009) Virus entry via the alternative coreceptors CCR3 and FPRL1 differs by human immunodeficiency virus type 1 subtype. J Virol 83(17):8353–8363

    CAS  PubMed  PubMed Central  Google Scholar 

  • Nottet HS, Persidsky Y, Sasseville VG, Nukuna AN, Bock P, Zhai QH et al (1996) Mechanisms for the transendothelial migration of HIV-1-infected monocytes into brain. J Immunol 156(3):1284–1295

    CAS  PubMed  Google Scholar 

  • Okafor CN, Zhou Z, Burrell LE 2nd, Kelso NE, Whitehead NE, Harman JS et al (2017) Marijuana use and viral suppression in persons receiving medical care for HIV-infection. Am J Drug Alcohol Abuse 43(1):103–110

    PubMed  Google Scholar 

  • Patro SC, Azzoni L, Joseph J, Fair MG, Sierra-Madero JG, Rassool MS et al (2016) Antiretroviral therapy in HIV-1-infected individuals with CD4 count below 100 cells/mm3 results in differential recovery of monocyte activation. J Leukoc Biol 100(1):223–231

    PubMed  Google Scholar 

  • Peluso MJ, Ferretti F, Peterson J, Lee E, Fuchs D, Boschini A et al (2012) Cerebrospinal fluid HIV escape associated with progressive neurologic dysfunction in patients on antiretroviral therapy with well controlled plasma viral load. AIDS 26(14):1765–1774

    CAS  PubMed  Google Scholar 

  • Peluso MJ, Meyerhoff DJ, Price RW, Peterson J, Lee E, Young AC et al (2013) Cerebrospinal fluid and neuroimaging biomarker abnormalities suggest early neurological injury in a subset of individuals during primary HIV infection. J Infect Dis 207(11):1703–1712

    CAS  PubMed  PubMed Central  Google Scholar 

  • Persidsky Y, Ghorpade A, Rasmussen J, Limoges J, Liu XJ, Stins M et al (1999) Microglial and astrocyte chemokines regulate monocyte migration through the blood-brain barrier in human immunodeficiency virus-1 encephalitis. Am J Pathol 155(5):1599–1611

    CAS  PubMed  PubMed Central  Google Scholar 

  • Pinacchio C, Scheri GC, Statzu M, Santinelli L, Ceccarelli G, Innocenti GP et al (2018) Type I/II interferon in HIV-1-infected patients: expression in gut mucosa and in peripheral blood mononuclear cells and its modification upon probiotic supplementation. J Immunol Res 2018:1738676

    PubMed  PubMed Central  Google Scholar 

  • Pinto-Sanchez MI, Hall GB, Ghajar K, Nardelli A, Bolino C, Lau JT et al (2017) Probiotic bifidobacterium longum NCC3001 reduces depression scores and alters brain activity: a pilot study in patients with irritable bowel syndrome. Gastroenterology 153(2):448–59.e8

    PubMed  Google Scholar 

  • Pistollato F, Sumalla Cano S, Elio I, Masias Vergara M, Giampieri F, Battino M (2016) Role of gut microbiota and nutrients in amyloid formation and pathogenesis of Alzheimer disease. Nutr Rev 74(10):624–634

    PubMed  Google Scholar 

  • Potula R, Hawkins BJ, Cenna JM, Fan S, Dykstra H, Ramirez SH et al (2010) Methamphetamine causes mitochondrial oxidative damage in human T lymphocytes leading to functional impairment. J Immunol 185(5):2867–2876

    CAS  PubMed  Google Scholar 

  • Pulliam L (2014) Cognitive consequences of a sustained monocyte type 1 IFN response in HIV-1 infection. Curr HIV Res 12(2):77–84

    CAS  PubMed  PubMed Central  Google Scholar 

  • Pulliam L, Gupta A (2015) Modulation of cellular function through immune-activated exosomes. DNA Cell Biol 34(7):459–463

    CAS  PubMed  PubMed Central  Google Scholar 

  • Pulliam L, Gascon R, Stubblebine M, McGuire D, McGrath MS (1997) Unique monocyte subset in patients with AIDS dementia. Lancet 349(9053):692–695

    CAS  PubMed  Google Scholar 

  • Pulliam L, Calosing C, Sun B, Grunfeld C, Rempel H (2014) Monocyte activation from interferon-alpha in HIV infection increases acetylated LDL uptake and ROS production. J Interferon Cytokine Res 34(10):822–828

    CAS  PubMed  PubMed Central  Google Scholar 

  • Pulliam L, Sun B, Mustapic M, Chawla S, Kapogiannis D (2019) Plasma neuronal exosomes serve as biomarkers of cognitive impairment in HIV infection and Alzheimer’s disease. J Neurovirol. https://doi.org/10.1007/s13365-018-0695-4

  • Rempel H, Calosing C, Sun B, Pulliam L (2008) Sialoadhesin expressed on IFN-induced monocytes binds HIV-1 and enhances infectivity. PLoS One 3(4):e1967

    PubMed  PubMed Central  Google Scholar 

  • Rempel H, Sun B, Calosing C, Pillai SK, Pulliam L (2010) Interferon-alpha drives monocyte gene expression in chronic unsuppressed HIV-1 infection. AIDS 24(10):1415–1423

    CAS  PubMed  Google Scholar 

  • Rempel H, Sun B, Calosing C, Abadjian L, Monto A, Pulliam L (2013) Monocyte activation in HIV/HCV coinfection correlates with cognitive impairment. PLoS One 8(2):e55776

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ribeiro A, Heimesaat MM, Bereswill S (2017) Changes of the intestinal microbiome-host homeostasis in HIV-infected individuals – a focus on the bacterial gut microbiome. Eur J Microbiol Immunol (Bp) 7(3):158–167

    CAS  Google Scholar 

  • Rizzo MD, Crawford RB, Henriquez JE, Aldhamen YA, Gulick P, Amalfitano A et al (2018) HIV-infected cannabis users have lower circulating CD16+ monocytes and IFN-gamma-inducible protein 10 levels compared with nonusing HIV patients. AIDS 32(4):419–429

    CAS  PubMed  Google Scholar 

  • Sami Saribas A, Cicalese S, Ahooyi TM, Khalili K, Amini S, Sariyer IK (2017) HIV-1 Nef is released in extracellular vesicles derived from astrocytes: evidence for Nef-mediated neurotoxicity. Cell Death Dis 8(1):e2542

    CAS  PubMed  PubMed Central  Google Scholar 

  • Sandler NG, Wand H, Roque A, Law M, Nason MC, Nixon DE et al (2011) Plasma levels of soluble CD14 independently predict mortality in HIV infection. J Infect Dis 203(6):780–790

    CAS  PubMed  PubMed Central  Google Scholar 

  • Savignac HM, Kiely B, Dinan TG, Cryan JF (2014) Bifidobacteria exert strain-specific effects on stress-related behavior and physiology in BALB/c mice. Neurogastroenterol Motil 26(11):1615–1627

    CAS  PubMed  Google Scholar 

  • Scagnolari C, Antonelli G (2018) Type I interferon and HIV: subtle balance between antiviral activity, immunopathogenesis and the microbiome. Cytokine Growth Factor Rev 40:19–31

    CAS  PubMed  PubMed Central  Google Scholar 

  • Serrano-Villar S, Sainz T, Ma ZM, Utay NS, Chun TW, Mann S et al (2016) Effects of combined CCR5/integrase inhibitors-based regimen on mucosal immunity in HIV-infected patients naive to antiretroviral therapy: a pilot randomized trial. PLoS Pathog 12(1):e1005381

    PubMed  PubMed Central  Google Scholar 

  • Soontornniyomkij V, Kesby JP, Morgan EE, Bischoff-Grethe A, Minassian A, Brown GG et al (2016) Effects of HIV and methamphetamine on brain and behavior: evidence from human studies and animal models. J Neuroimmune Pharmacol 11(3):495–510

    PubMed  PubMed Central  Google Scholar 

  • Sun B, Abadjian L, Rempel H, Calosing C, Rothlind J, Pulliam L (2010) Peripheral biomarkers do not correlate with cognitive impairment in highly active antiretroviral therapy-treated subjects with human immunodeficiency virus type 1 infection. J Neurovirol 16(2):115–124

    CAS  PubMed  Google Scholar 

  • Sun B, Dalvi P, Abadjian L, Tang N, Pulliam L (2017) Blood neuron-derived exosomes as biomarkers of cognitive impairment in HIV. AIDS 31(14):F9–F17

    CAS  PubMed  Google Scholar 

  • Sun B, Fernandes N, Pulliam L (2019) Profile of neuronal exosomes in HIV cognitive impairment exposes gender differences. AIDS. https://doi.org/10.1097/QAD.0000000000002272. [Epub ahead of print]

  • Tang N, Sun B, Gupta A, Rempel H, Pulliam L (2016) Monocyte exosomes induce adhesion molecules and cytokines via activation of NF-kappaB in endothelial cells. FASEB J 30(9):3097–3106

    CAS  PubMed  PubMed Central  Google Scholar 

  • Thames AD, Mahmood Z, Burggren AC, Karimian A, Kuhn TP (2016) Combined effects of HIV and marijuana use on neurocognitive functioning and immune status. AIDS Care 28(5):628–632

    PubMed  Google Scholar 

  • Tozzi V, Balestra P, Salvatori MF, Vlassi C, Liuzzi G, Giancola ML et al (2009) Changes in cognition during antiretroviral therapy: comparison of 2 different ranking systems to measure antiretroviral drug efficacy on HIV-associated neurocognitive disorders. J Acquir Immune Defic Syndr 52(1):56–63

    CAS  PubMed  Google Scholar 

  • Treisman GJ, Soudry O (2016) Neuropsychiatric effects of HIV antiviral medications. Drug Saf 39(10):945–957

    CAS  PubMed  Google Scholar 

  • UNAIDS (2018) Global HIV & AIDS statistics – 2018 fact sheet

    Google Scholar 

  • Var SR, Day TR, Vitomirov A, Smith DM, Soontornniyomkij V, Moore DJ et al (2016) Mitochondrial injury and cognitive function in HIV infection and methamphetamine use. AIDS 30(6):839–848

    CAS  PubMed  Google Scholar 

  • Veenstra M, Leon-Rivera R, Li M, Gama L, Clements JE, Berman JW (2017) Mechanisms of CNS viral seeding by HIV(+) CD14(+) CD16(+) monocytes: establishment and reseeding of viral reservoirs contributing to HIV-associated neurocognitive disorders. MBio 8(5). pii: e01280-17

    Google Scholar 

  • Volkow ND, Chang L, Wang GJ, Fowler JS, Franceschi D, Sedler M et al (2001) Loss of dopamine transporters in methamphetamine abusers recovers with protracted abstinence. J Neurosci 21(23):9414–9418

    CAS  PubMed  PubMed Central  Google Scholar 

  • Walsh JG, Reinke SN, Mamik MK, McKenzie BA, Maingat F, Branton WG et al (2014) Rapid inflammasome activation in microglia contributes to brain disease in HIV/AIDS. Retrovirology 11:35

    PubMed  PubMed Central  Google Scholar 

  • Watkins CC, Treisman GJ (2015) Cognitive impairment in patients with AIDS – prevalence and severity. HIV AIDS (Auckl) 7:35–47

    Google Scholar 

  • Weber E, Blackstone K, Woods SP (2013) Cognitive neurorehabilitation of HIV-associated neurocognitive disorders: a qualitative review and call to action. Neuropsychol Rev 23(1):81–98

    PubMed  PubMed Central  Google Scholar 

  • Winston CN, Goetzl EJ, Akers JC, Carter BS, Rockenstein EM, Galasko D et al (2016) Prediction of conversion from mild cognitive impairment to dementia with neuronally derived blood exosome protein profile. Alzheimers Dement (Amst) 3:63–72

    Google Scholar 

  • Woods SP, Moore DJ, Weber E, Grant I (2009) Cognitive neuropsychology of HIV-associated neurocognitive disorders. Neuropsychol Rev 19(2):152–168

    PubMed  PubMed Central  Google Scholar 

  • Xu E, Liu J, Liu H, Wang X, Xiong H (2017) Role of microglia in methamphetamine-induced neurotoxicity. Int J Physiol Pathophysiol Pharmacol 9(3):84–100

    CAS  PubMed  PubMed Central  Google Scholar 

  • Yeung MC, Pulliam L, Lau AS (1995) The HIV envelope protein gp120 is toxic to human brain-cell cultures through the induction of interleukin-6 and tumor necrosis factor-alpha. AIDS 9(2):137–143

    CAS  PubMed  Google Scholar 

  • Zhen A, Krutzik SR, Levin BR, Kasparian S, Zack JA, Kitchen SG (2014) CD4 ligation on human blood monocytes triggers macrophage differentiation and enhances HIV infection. J Virol 88(17):9934–9946

    PubMed  PubMed Central  Google Scholar 

  • Zhong Y, Hennig B, Toborek M (2010) Intact lipid rafts regulate HIV-1 Tat protein-induced activation of the Rho signaling and upregulation of P-glycoprotein in brain endothelial cells. J Cereb Blood Flow Metab 30(3):522–533

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Laboratory Medicine, San Francisco VA Health Care System, San Francisco, CA, USA

    Nicole Fernandes & Lynn Pulliam

  2. University of California, San Francisco, San Francisco, CA, USA

    Nicole Fernandes & Lynn Pulliam

Authors
  1. Nicole Fernandes
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lynn Pulliam
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Lynn Pulliam .

Editor information

Editors and Affiliations

  1. School of Psychology, The University of New South Wales, Sydney, NSW, Australia

    Lucette A. Cysique

  2. MAP Centre for Urban Health Solutions, Li Ka Shing Knowledge Institute St. Michael’s Hospital and Unity Health Toronto, Toronto, ON, Canada

    Sean B. Rourke

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Fernandes, N., Pulliam, L. (2019). Inflammatory Mechanisms and Cascades Contributing to Neurocognitive Impairment in HIV/AIDS. In: Cysique, L.A., Rourke, S.B. (eds) Neurocognitive Complications of HIV-Infection. Current Topics in Behavioral Neurosciences, vol 50. Springer, Cham. https://doi.org/10.1007/7854_2019_100

Download citation

Publish with us

Policies and ethics

Search

Navigation