Skip to main content

Advertisement

SpringerLink
Log in

Role of mu-opioids as cofactors in human immunodeficiency virus type 1 disease progression and neuropathogenesis

  • Mini review
  • Published:
Journal of NeuroVirology Aims and scope Submit manuscript

Abstract

About one third of acquired immunodeficiency syndrome cases in the USA have been attributed to the use of injected addictive drugs, frequently involving opioids like heroin and morphine, establishing them as significant predisposing risk factors for contracting human immunodeficiency virus type 1 (HIV-1). Accumulating evidence from in vitro and in vivo experimental systems indicates that opioids act in concert with HIV-1 proteins to exacerbate dysregulation of neural and immune cell function and survival through diverse molecular mechanisms. In contrast, the impact of opioid exposure and withdrawal on the viral life cycle and HIV-1 disease progression itself is unclear, with conflicting reports emerging from the simian immunodeficiency virus and simian–human immunodeficiency virus infection models. However, these studies suggest a potential role of opioids in elevated viral production. Because human microglia, astrocytes, CD4+ T lymphocytes, and monocyte-derived macrophages express opioid receptors, it is likely that intracellular signaling events triggered by morphine facilitate enhancement of HIV-1 infection in these target cell populations. This review highlights the biochemical changes that accompany prolonged exposure to and withdrawal from morphine that synergize with HIV-1 proteins to disrupt normal cellular physiological functions especially within the central nervous system. More importantly, it collates evidence from epidemiological studies, animal models, and heterologous cell systems to propose a mechanistic link between such physiological adaptations and direct modulation of HIV-1 production. Understanding the opioid–HIV-1 interface at the molecular level is vitally important in designing better treatment strategies for HIV-1-infected patients who abuse opioids.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Alexaki A, Wigdahl B (2008) HIV-1 infection of bone marrow hematopoietic progenitor cells and their role in trafficking and viral dissemination. PLoS Pathog 4:e1000215

    Article  PubMed  CAS  Google Scholar 

  • Alexaki A, Liu Y, Wigdahl B (2008) Cellular reservoirs of HIV-1 and their role in viral persistence. Curr HIV Res 6:388–400

    Article  PubMed  CAS  Google Scholar 

  • Avdoshina V, Biggio F, Palchik G, Campbell LA, Mocchetti I (2010) Morphine induces the release of CCL5 from astrocytes: potential neuroprotective mechanism against the HIV protein gp120. Glia 58:1630–1639

    PubMed  Google Scholar 

  • Banerjee A, Pirrone V, Wigdahl B, Nonnemacher MR (2011) Transcriptional regulation of the chemokine co-receptor CCR5 by the cAMP/PKA/CREB pathway. Biomedicine and Pharmacotherapy. doi:10.1016/j.biopha.2011.03.009

  • Belcheva MM, Szucs M, Wang D, Sadee W, Coscia CJ (2001) mu-Opioid receptor-mediated ERK activation involves calmodulin-dependent epidermal growth factor receptor transactivation. J Biol Chem 276:33847–33853

    Article  PubMed  CAS  Google Scholar 

  • Bell JE, Arango JC, Robertson R, Brettle RP, Leen C, Simmonds P (2002) HIV and drug misuse in the Edinburgh cohort. J Acquir Immune Defic Syndr 31(Suppl 2):S35–S42

    PubMed  CAS  Google Scholar 

  • Bokhari SM, Yao H, Bethel-Brown C, Fuwang P, Williams R, Dhillon NK, Hegde R, Kumar A, Buch SJ (2009) Morphine enhances Tat-induced activation in murine microglia. J Neurovirol 15:219–228

    Article  PubMed  CAS  Google Scholar 

  • Bokhari SM, Hegde R, Callen S, Yao H, Adany I, Li Q, Li Z, Pinson D, Yeh HW, Cheney PD, Buch S (2011). Morphine potentiates neuropathogenesis of SIV infection in rhesus macaques. J Neuroimmune Pharmacol. doi:10.1007/s11481-011-9272-9

  • Bruce-Keller AJ, Turchan-Cholewo J, Smart EJ, Geurin T, Chauhan A, Reid R, Xu R, Nath A, Knapp PE, Hauser KF (2008) Morphine causes rapid increases in glial activation and neuronal injury in the striatum of inducible HIV-1 Tat transgenic mice. Glia 56:1414–1427

    Article  PubMed  Google Scholar 

  • Burdo TH, Soulas C, Orzechowski K, Button J, Krishnan A, Sugimoto C, Alvarez X, Kuroda MJ, Williams KC (2010) Increased monocyte turnover from bone marrow correlates with severity of SIV encephalitis and CD163 levels in plasma. PLoS Pathog 6:e1000842

    Article  PubMed  CAS  Google Scholar 

  • Carter CC, Onafuwa-Nuga A, McNamara LA, Jt R, Bixby D, Savona MR, Collins KL (2010) HIV-1 infects multipotent progenitor cells causing cell death and establishing latent cellular reservoirs. Nat Med 16:446–451

    Article  PubMed  CAS  Google Scholar 

  • Chao J, Nestler EJ (2004) Molecular neurobiology of drug addiction. Annu Rev Med 55:113–132

    Article  PubMed  CAS  Google Scholar 

  • Chao CC, Gekker G, Hu S, Sheng WS, Portoghese PS, Peterson PK (1995) Upregulation of HIV-1 expression in cocultures of chronically infected promonocytes and human brain cells by dynorphin. Biochem Pharmacol 50:715–722

    Article  PubMed  CAS  Google Scholar 

  • Chao CC, Hu S, Shark KB, Sheng WS, Gekker G, Peterson PK (1997) Activation of mu opioid receptors inhibits microglial cell chemotaxis. J Pharmacol Exp Ther 281:998–1004

    PubMed  CAS  Google Scholar 

  • Chuang LF, Killam KF Jr, Chuang RY (1993) Increased replication of simian immunodeficiency virus in CEM x174 cells by morphine sulfate. Biochem Biophys Res Commun 195:1165–1173

    Article  PubMed  CAS  Google Scholar 

  • Chuang TK, Killam KF Jr, Chuang LF, Kung HF, Sheng WS, Chao CC, Yu L, Chuang RY (1995) Mu opioid receptor gene expression in immune cells. Biochem Biophys Res Commun 216:922–930

    Article  PubMed  CAS  Google Scholar 

  • Chuang RY, Suzuki S, Chuang TK, Miyagi T, Chuang LF, Doi RH (2005) Opioids and the progression of simian AIDS. Front Biosci 10:1666–1677

    Article  PubMed  CAS  Google Scholar 

  • Clements JE, Gama L, Graham DR, Mankowski JL, Zink MC (2011) A simian immunodeficiency virus macaque model of highly active antiretroviral treatment: viral latency in the periphery and the central nervous system. Curr Opin HIV AIDS 6:37–42

    Article  PubMed  Google Scholar 

  • Clinic C (2010). Heroin: abuse and addiction. Cleveland. http://my.clevelandclinic.org/disorders/heroin_addiction/hic_heroin_abuse_and_addiction.aspx

  • Cristillo AD, Highbarger HC, Dewar RL, Dimitrov DS, Golding H, Bierer BE (2002a) Up-regulation of HIV coreceptor CXCR4 expression in human T lymphocytes is mediated in part by a cAMP-responsive element. FASEB J 16:354–364

    Article  PubMed  CAS  Google Scholar 

  • Cristillo AD, Xiao X, Campbell-Malone R, Dimitrov DS, Bierer BE (2002b) Differences between CEM and human peripheral blood T lymphocytes in cAMP-dependent HIV viral fusion and CXCR4 expression. Exp Mol Pathol 73:9–18

    Article  PubMed  CAS  Google Scholar 

  • Dhawan BN, Cesselin F, Raghubir R, Reisine T, Bradley PB, Portoghese PS, Hamon M (1996) International union of pharmacology. XII. Classification of opioid receptors. Pharmacol Rev 48:567–592

    PubMed  CAS  Google Scholar 

  • Donahoe RM (2004) Multiple ways that drug abuse might influence AIDS progression: clues from a monkey model. J Neuroimmunol 147:28–32

    Article  PubMed  CAS  Google Scholar 

  • Donahoe RM, Vlahov D (1998) Opiates as potential cofactors in progression of HIV-1 infections to AIDS. J Neuroimmunol 83:77–87

    Article  PubMed  CAS  Google Scholar 

  • Donahoe RM, Byrd LD, McClure HM, Fultz P, Brantley M, Marsteller F, Ansari AA, Wenzel D, Aceto M (1993) Consequences of opiate-dependency in a monkey model of AIDS. Adv Exp Med Biol 335:21–28

    PubMed  CAS  Google Scholar 

  • El-Hage N, Gurwell JA, Singh IN, Knapp PE, Nath A, Hauser KF (2005) Synergistic increases in intracellular Ca2+, and the release of MCP-1, RANTES, and IL-6 by astrocytes treated with opiates and HIV-1 Tat. Glia 50:91–106

    Article  PubMed  Google Scholar 

  • El-Hage N, Bruce-Keller AJ, Yakovleva T, Bazov I, Bakalkin G, Knapp PE, Hauser KF (2008) Morphine exacerbates HIV-1 Tat-induced cytokine production in astrocytes through convergent effects on [Ca(2+)](i). NF-kappaB trafficking and transcription. PLoS ONE 3:e4093

    Article  PubMed  CAS  Google Scholar 

  • Eugenin EA, D’Aversa TG, Lopez L, Calderon TM, Berman JW (2003) MCP-1 (CCL2) protects human neurons and astrocytes from NMDA or HIV-tat-induced apoptosis. J Neurochem 85:1299–1311

    Article  PubMed  CAS  Google Scholar 

  • Faragon JJ, Piliero PJ (2003) Drug interactions associated with HAART: focus on treatments for addiction and recreational drugs. AIDS Read 13:433–434, 437–41, 446–50

    PubMed  Google Scholar 

  • Fredriksson R, Lagerstrom MC, Lundin LG, Schioth HB (2003) The G-protein-coupled receptors in the human genome form five main families. Phylogenetic analysis, paralogon groups, and fingerprints. Mol Pharmacol 63:1256–1272

    Article  PubMed  CAS  Google Scholar 

  • Fukuda K, Kato S, Morikawa H, Shoda T, Mori K (1996) Functional coupling of the delta-, mu-, and kappa-opioid receptors to mitogen-activated protein kinase and arachidonate release in Chinese hamster ovary cells. J Neurochem 67:1309–1316

    Article  PubMed  CAS  Google Scholar 

  • Gonzalez GA, Montminy MR (1989) Cyclic AMP stimulates somatostatin gene transcription by phosphorylation of CREB at serine 133. Cell 59:675–680

    Article  PubMed  CAS  Google Scholar 

  • Guo CJ, Li Y, Tian S, Wang X, Douglas SD, Ho WZ (2002) Morphine enhances HIV infection of human blood mononuclear phagocytes through modulation of beta-chemokines and CCR5 receptor. J Investig Med 50:435–442

    Article  PubMed  CAS  Google Scholar 

  • Gurwell JA, Nath A, Sun Q, Zhang J, Martin KM, Chen Y, Hauser KF (2001) Synergistic neurotoxicity of opioids and human immunodeficiency virus-1 Tat protein in striatal neurons in vitro. Neuroscience 102:555–563

    Article  PubMed  CAS  Google Scholar 

  • Hauser KF, El-Hage N, Buch S, Berger JR, Tyor WR, Nath A, Bruce-Keller AJ, Knapp PE (2005) Molecular targets of opiate drug abuse in neuroAIDS. Neurotox Res 8:63–80

    Article  PubMed  CAS  Google Scholar 

  • Hauser KF, El-Hage N, Buch S, Nath A, Tyor WR, Bruce-Keller AJ, Knapp PE (2006) Impact of opiate-HIV-1 interactions on neurotoxic signaling. J Neuroimmune Pharmacol 1:98–105

    Article  PubMed  Google Scholar 

  • Henry DJ, Grandy DK, Lester HA, Davidson N, Chavkin C (1995) Kappa-opioid receptors couple to inwardly rectifying potassium channels when coexpressed by Xenopus oocytes. Mol Pharmacol 47:551–557

    PubMed  CAS  Google Scholar 

  • Hu S, Sheng WS, Lokensgard JR, Peterson PK (2005) Morphine potentiates HIV-1 gp120-induced neuronal apoptosis. J Infect Dis 191:886–889

    Article  PubMed  CAS  Google Scholar 

  • Jessop JJ, Taplits MS (1991) Effect of high doses of morphine on Con-A induced lymphokine production in vitro. Immunopharmacology 22:175–184

    Article  PubMed  CAS  Google Scholar 

  • Kaul M, Lipton SA (2004) Signaling pathways to neuronal damage and apoptosis in human immunodeficiency virus type 1-associated dementia: chemokine receptors, excitotoxicity, and beyond. J Neurovirol 10(Suppl 1):97–101

    PubMed  CAS  Google Scholar 

  • Kaul M, Lipton SA (2006) Mechanisms of neuroimmunity and neurodegeneration associated with HIV-1 infection and AIDS. J Neuroimmune Pharmacol 1:138–151

    Article  PubMed  Google Scholar 

  • Kaul M, Garden GA, Lipton SA (2001) Pathways to neuronal injury and apoptosis in HIV-associated dementia. Nature 410:988–994

    Article  PubMed  CAS  Google Scholar 

  • Kee BL, Arias J, Montminy MR (1996) Adaptor-mediated recruitment of RNA polymerase II to a signal-dependent activator. J Biol Chem 271:2373–2375

    Article  PubMed  CAS  Google Scholar 

  • Khalap A, Bagrosky B, Lecaude S, Youson J, Danielson P, Dores RM (2005) Trends in the evolution of the proenkephalin and prodynorphin genes in gnathostomes. Ann N Y Acad Sci 1040:22–37

    Article  PubMed  CAS  Google Scholar 

  • Korzus E, Torchia J, Rose DW, Xu L, Kurokawa R, McInerney EM, Mullen TM, Glass CK, Rosenfeld MG (1998) Transcription factor-specific requirements for coactivators and their acetyltransferase functions. Science 279:703–707

    Article  PubMed  CAS  Google Scholar 

  • Krebs FC, Goodenow MM, Wigdahl B (1997) Neuroglial ATF/CREB factors interact with the human immunodeficiency virus type 1 long terminal repeat. J Neurovirol 3(Suppl 1):S28–S32

    PubMed  Google Scholar 

  • Krebs FC, Mehrens D, Pomeroy S, Goodenow MM, Wigdahl B (1998) Human immunodeficiency virus type 1 long terminal repeat quasispecies differ in basal transcription and nuclear factor recruitment in human glial cells and lymphocytes. J Biomed Sci 5:31–44

    Article  PubMed  CAS  Google Scholar 

  • Kuipers HF, Biesta PJ, Montagne LJ, van Haastert ES, van der Valk P, van den Elsen PJ (2008) CC chemokine receptor 5 gene promoter activation by the cyclic AMP response element binding transcription factor. Blood 112:1610–1619

    Article  PubMed  CAS  Google Scholar 

  • Kumar R, Torres C, Yamamura Y, Rodriguez I, Martinez M, Staprans S, Donahoe RM, Kraiselburd E, Stephens EB, Kumar A (2004) Modulation by morphine of viral set point in rhesus macaques infected with simian immunodeficiency virus and simian-human immunodeficiency virus. J Virol 78:11425–11428

    Article  PubMed  CAS  Google Scholar 

  • Kumar R, Orsoni S, Norman L, Verma AS, Tirado G, Giavedoni LD, Staprans S, Miller GM, Buch SJ, Kumar A (2006) Chronic morphine exposure causes pronounced virus replication in cerebral compartment and accelerated onset of AIDS in SIV/SHIV-infected Indian rhesus macaques. Virology 354:192–206

    Article  PubMed  CAS  Google Scholar 

  • Kwok RP, Lundblad JR, Chrivia JC, Richards JP, Bachinger HP, Brennan RG, Roberts SG, Green MR, Goodman RH (1994) Nuclear protein CBP is a coactivator for the transcription factor CREB. Nature 370:223–226

    Article  PubMed  CAS  Google Scholar 

  • Lane-Ladd SB, Pineda J, Boundy VA, Pfeuffer T, Krupinski J, Aghajanian GK, Nestler EJ (1997) CREB (cAMP response element-binding protein) in the locus coeruleus: biochemical, physiological, and behavioral evidence for a role in opiate dependence. J Neurosci 17:7890–7901

    PubMed  CAS  Google Scholar 

  • Law PY, Wong YH, Loh HH (2000) Molecular mechanisms and regulation of opioid receptor signaling. Annu Rev Pharmacol Toxicol 40:389–430

    Article  PubMed  CAS  Google Scholar 

  • Law PY, Loh HH, Wei LN (2004) Insights into the receptor transcription and signaling: implications in opioid tolerance and dependence. Neuropharmacology 47(Suppl 1):300–311

    Article  PubMed  CAS  Google Scholar 

  • Li Y, Merrill JD, Mooney K, Song L, Wang X, Guo CJ, Savani RC, Metzger DS, Douglas SD, Ho WZ (2003) Morphine enhances HIV infection of neonatal macrophages. Pediatr Res 54:282–288

    Article  PubMed  CAS  Google Scholar 

  • Liu JG, Anand KJ (2001) Protein kinases modulate the cellular adaptations associated with opioid tolerance and dependence. Brain Res Brain Res Rev 38:1–19

    Article  PubMed  CAS  Google Scholar 

  • Liu Y, Tang XP, McArthur JC, Scott J, Gartner S (2000) Analysis of human immunodeficiency virus type 1 gp160 sequences from a patient with HIV dementia: evidence for monocyte trafficking into brain. J Neurovirol 6(Suppl 1):S70–S81

    PubMed  CAS  Google Scholar 

  • Mahajan SD, Aalinkeel R, Reynolds JL, Nair BB, Fernandez SF, Schwartz SA, Nair MP (2005) Morphine exacerbates HIV-1 viral protein gp120 induced modulation of chemokine gene expression in U373 astrocytoma cells. Curr HIV Res 3:277–288

    Article  PubMed  CAS  Google Scholar 

  • Martin-Kleiner I, Gabrilovac J, Boranić M (2004) Opioids as growth regulators of normal and malignant immunohaematopoiesis—a review. Haema 7:287–295

    CAS  Google Scholar 

  • McCarthy L, Wetzel M, Sliker JK, Eisenstein TK, Rogers TJ (2001) Opioids, opioid receptors, and the immune response. Drug Alcohol Depend 62:111–123

    Article  PubMed  CAS  Google Scholar 

  • McElrath MJ, Pruett JE, Cohn ZA (1989) Mononuclear phagocytes of blood and bone marrow: comparative roles as viral reservoirs in human immunodeficiency virus type 1 infections. Proc Natl Acad Sci USA 86:675–679

    Article  PubMed  CAS  Google Scholar 

  • McNamara LA, Collins KL (2011) Hematopoietic stem/precursor cells as HIV reservoirs. Curr Opin HIV AIDS 6:43–48

    Article  PubMed  Google Scholar 

  • Merg F, Filliol D, Usynin I, Bazov I, Bark N, Hurd YL, Yakovleva T, Kieffer BL, Bakalkin G (2006) Big dynorphin as a putative endogenous ligand for the kappa-opioid receptor. J Neurochem 97:292–301

    Article  PubMed  CAS  Google Scholar 

  • Montagne J, Beraud C, Crenon I, Lombard-Platet G, Gazzolo L, Sergeant A, Jalinot P (1990) Tax1 induction of the HTLV-I 21 bp enhancer requires cooperation between two cellular DNA-binding proteins. EMBO J 9:957–964

    PubMed  CAS  Google Scholar 

  • Nakajima T, Uchida C, Anderson SF, Parvin JD, Montminy M (1997) Analysis of a cAMP-responsive activator reveals a two-component mechanism for transcriptional induction via signal-dependent factors. Genes Dev 11:738–747

    Article  PubMed  CAS  Google Scholar 

  • Nath A (1999) Pathobiology of human immunodeficiency virus dementia. Semin Neurol 19:113–127

    Article  PubMed  CAS  Google Scholar 

  • Nath A, Hauser KF, Wojna V, Booze RM, Maragos W, Prendergast M, Cass W, Turchan JT (2002) Molecular basis for interactions of HIV and drugs of abuse. J Acquir Immune Defic Syndr 31(Suppl 2):S62–S69

    PubMed  CAS  Google Scholar 

  • Nestler EJ (1997) Molecular mechanisms of opiate and cocaine addiction. Curr Opin Neurobiol 7:713–719

    Article  PubMed  CAS  Google Scholar 

  • Nestler EJ (2001) Molecular basis of long-term plasticity underlying addiction. Nat Rev Neurosci 2:119–128

    Article  PubMed  CAS  Google Scholar 

  • Nestler EJ, Aghajanian GK (1997) Molecular and cellular basis of addiction. Science 278:58–63

    Article  PubMed  CAS  Google Scholar 

  • Ozawa T, Nakagawa T, Minami M, Satoh M (1999) Supersensitization of the adenylyl cyclase system in Chinese hamster ovary cells co-expressing cloned opioid receptors and Gz, a PTX-insensitive G protein. Neurosci Lett 267:117–120

    Article  PubMed  CAS  Google Scholar 

  • Pan YX (2003) Identification of alternatively spliced variants from opioid receptor genes. Methods Mol Med 84:65–75

    PubMed  CAS  Google Scholar 

  • Pan YX, Xu J, Bolan E, Chang A, Mahurter L, Rossi G, Pasternak GW (2000) Isolation and expression of a novel alternatively spliced mu opioid receptor isoform, MOR-1 F. FEBS Lett 466:337–340

    Article  PubMed  CAS  Google Scholar 

  • Parker D, Ferreri K, Nakajima T, LaMorte VJ, Evans R, Koerber SC, Hoeger C, Montminy MR (1996) Phosphorylation of CREB at Ser-133 induces complex formation with CREB-binding protein via a direct mechanism. Mol Cell Biol 16:694–703

    PubMed  CAS  Google Scholar 

  • Patel JP, Sengupta R, Bardi G, Khan MZ, Mullen-Przeworski A, Meucci O (2006) Modulation of neuronal CXCR4 by the micro-opioid agonist DAMGO. J Neurovirol 12:492–500

    Article  PubMed  CAS  Google Scholar 

  • Perez DM (2003) The evolutionarily triumphant G-protein-coupled receptor. Mol Pharmacol 63:1202–1205

    Article  PubMed  CAS  Google Scholar 

  • Persidsky Y, Gendelman HE (2003) Mononuclear phagocyte immunity and the neuropathogenesis of HIV-1 infection. J Leukoc Biol 74:691–701

    Article  PubMed  CAS  Google Scholar 

  • Pert CB, Snyder SH (1973) Properties of opiate-receptor binding in rat brain. Proc Natl Acad Sci USA 70:2243–2247

    Article  PubMed  CAS  Google Scholar 

  • Peterson PK, Sharp BM, Gekker G, Portoghese PS, Sannerud K, Balfour HH Jr (1990) Morphine promotes the growth of HIV-1 in human peripheral blood mononuclear cell cocultures. AIDS 4:869–873

    Article  PubMed  CAS  Google Scholar 

  • Peterson PK, Gekker G, Hu S, Anderson WR, Kravitz F, Portoghese PS, Balfour HH Jr, Chao CC (1994) Morphine amplifies HIV-1 expression in chronically infected promonocytes cocultured with human brain cells. J Neuroimmunol 50:167–175

    Article  PubMed  CAS  Google Scholar 

  • Peterson PK, Gekker G, Hu S, Lokensgard J, Portoghese PS, Chao CC (1999) Endomorphin-1 potentiates HIV-1 expression in human brain cell cultures: implication of an atypical mu-opioid receptor. Neuropharmacology 38:273–278

    Article  PubMed  CAS  Google Scholar 

  • Piros ET, Prather PL, Loh HH, Law PY, Evans CJ, Hales TG (1995) Ca2+ channel and adenylyl cyclase modulation by cloned mu-opioid receptors in GH3 cells. Mol Pharmacol 47:1041–1049

    PubMed  CAS  Google Scholar 

  • Pitcher J, Shimizu S, Burbassi S, Meucci O (2010) Disruption of neuronal CXCR4 function by opioids: preliminary evidence of ferritin heavy chain as a potential etiological agent in neuroAIDS. J Neuroimmunol 224:66–71

    Article  PubMed  CAS  Google Scholar 

  • Pleuvry BJ (1991) Opioid receptors and their ligands: natural and unnatural. Br J Anaesth 66:370–380

    Article  PubMed  CAS  Google Scholar 

  • Rahim RT, Feng P, Meissler JJ, Rogers TJ, Zhang L, Adler MW, Eisenstein TK (2004) Paradoxes of immunosuppression in mouse models of withdrawal. J Neuroimmunol 147:114–120

    Article  PubMed  CAS  Google Scholar 

  • Regez RM, Kleipool AE, Speekenbrink RG, Frissen PH (2005) The risk of needle stick accidents during surgical procedures: HIV-1 viral load in blood and bone marrow. Int J STD AIDS 16:671–672

    Article  PubMed  Google Scholar 

  • Reynolds JL, Mahajan SD, Sykes D, Nair MP (2006) Heroin-induces differential protein expression by normal human astrocytes (NHA). Am J Infect Dis 2:49–57

    Article  PubMed  CAS  Google Scholar 

  • Ronald PJ, Robertson JR, Elton RA (1994) Continued drug use and other cofactors for progression to AIDS among injecting drug users. AIDS 8:339–343

    Article  PubMed  CAS  Google Scholar 

  • Ross HL, Nonnemacher MR, Hogan TH, Quiterio SJ, Henderson A, McAllister JJ, Krebs FC, Wigdahl B (2001) Interaction between CCAAT/enhancer binding protein and cyclic AMP response element binding protein 1 regulates human immunodeficiency virus type 1 transcription in cells of the monocyte/macrophage lineage. J Virol 75:1842–1856

    Article  PubMed  CAS  Google Scholar 

  • Ruzicka BB, Fox CA, Thompson RC, Meng F, Watson SJ, Akil H (1995) Primary astroglial cultures derived from several rat brain regions differentially express mu, delta and kappa opioid receptor mRNA. Brain Res Mol Brain Res 34:209–220

    Article  PubMed  CAS  Google Scholar 

  • Sawaya BE, Deshmane SL, Mukerjee R, Fan S, Khalili K (2009) TNF alpha production in morphine-treated human neural cells is NF-kappaB-dependent. J Neuroimmune Pharmacol 4:140–149

    Article  PubMed  Google Scholar 

  • Sengupta R, Burbassi S, Shimizu S, Cappello S, Vallee RB, Rubin JB, Meucci O (2009) Morphine increases brain levels of ferritin heavy chain leading to inhibition of CXCR4-mediated survival signaling in neurons. J Neurosci 29:2534–2544

    Article  PubMed  CAS  Google Scholar 

  • Spencer RJ, Jin W, Thayer SA, Chakrabarti S, Law PY, Loh HH (1997) Mobilization of Ca2+ from intracellular stores in transfected neuro2a cells by activation of multiple opioid receptor subtypes. Biochem Pharmacol 54:809–818

    Article  PubMed  CAS  Google Scholar 

  • Steele AD, Henderson EE, Rogers TJ (2003) Mu-opioid modulation of HIV-1 coreceptor expression and HIV-1 replication. Virology 309:99–107

    Article  PubMed  CAS  Google Scholar 

  • Steidl U, Bork S, Schaub S, Selbach O, Seres J, Aivado M, Schroeder T, Rohr UP, Fenk R, Kliszewski S, Maercker C, Neubert P, Bornstein SR, Haas HL, Kobbe G, Tenen DG, Haas R, Kronenwett R (2004) Primary human CD34+ hematopoietic stem and progenitor cells express functionally active receptors of neuromediators. Blood 104:81–88

    Article  PubMed  CAS  Google Scholar 

  • Stiene-Martin A, Zhou R, Hauser KF (1998) Regional, developmental, and cell cycle-dependent differences in mu, delta, and kappa-opioid receptor expression among cultured mouse astrocytes. Glia 22:249–259

    Article  PubMed  CAS  Google Scholar 

  • Tai YH, Wang YH, Wang JJ, Tao PL, Tung CS, Wong CS (2006) Amitriptyline suppresses neuroinflammation and up-regulates glutamate transporters in morphine-tolerant rats. Pain 124:77–86

    Article  PubMed  CAS  Google Scholar 

  • Tallent M, Dichter MA, Bell GI, Reisine T (1994) The cloned kappa opioid receptor couples to an N-type calcium current in undifferentiated PC-12 cells. Neuroscience 63:1033–1040

    Article  PubMed  CAS  Google Scholar 

  • Wang J, Barke RA, Charboneau R, Roy S (2005) Morphine impairs host innate immune response and increases susceptibility to Streptococcus pneumoniae lung infection. J Immunol 174:426–434

    PubMed  CAS  Google Scholar 

  • Watts VJ (2002) Molecular mechanisms for heterologous sensitization of adenylate cyclase. J Pharmacol Exp Ther 302:1–7

    Article  PubMed  CAS  Google Scholar 

  • Wei LN, Loh HH (2002) Regulation of opioid receptor expression. Curr Opin Pharmacol 2:69–75

    Article  PubMed  CAS  Google Scholar 

  • Wiley CA, Soontornniyomkij V, Radhakrishnan L, Masliah E, Mellors J, Hermann SA, Dailey P, Achim CL (1998) Distribution of brain HIV load in AIDS. Brain Pathol 8:277–284

    Article  PubMed  CAS  Google Scholar 

  • Zadina JE, Hackler L, Ge LJ, Kastin AJ (1997) A potent and selective endogenous agonist for the mu-opiate receptor. Nature 386:499–502

    Article  PubMed  CAS  Google Scholar 

  • Zimprich A, Simon T, Hollt V (1995) Cloning and expression of an isoform of the rat mu opioid receptor (rMOR1B) which differs in agonist induced desensitization from rMOR1. FEBS Lett 359:142–146

    Article  PubMed  CAS  Google Scholar 

  • Zin CS, Nissen LM, O’Callaghan JP, Moore BJ, Smith MT (2010) Preliminary study of the plasma and cerebrospinal fluid concentrations of IL-6 and IL-10 in patients with chronic pain receiving intrathecal opioid infusions by chronically implanted pump for pain management. Pain Med 11:550–561

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

Dr. Michael Nonnemacher was supported by faculty development funds provided by the Department of Microbiology and Immunology and the Institute for Molecular Medicine and Infectious Disease. Dr. Brian Wigdahl was supported in part by funds from the Public Health Service, National Institutes of Health through grants from the National Institute of Neurological Disorders and Stroke, NS32092 and NS46263, the National Institute of Drug Abuse, DA19807 (Dr. Brian Wigdahl, Principal Investigator). Dr. Olimpia Meucci was supported in part by funds from the Public Health Service, National Institutes of Health through grants from the National Institute of Drug Abuse, DA19808 and DA15014 (Dr. Olimpia Meucci, Principal Investigator).

Marianne Strazza was supported by a Ruth L. Kirschstein National Research Service Award 5T32MH079785. The contents of this review are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health.

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Microbiology and Immunology, Drexel University College of Medicine, 245 N. 15th St., Philadelphia, PA, 19102, USA

    Anupam Banerjee, Marianne Strazza, Brian Wigdahl, Vanessa Pirrone, Olimpia Meucci & Michael R. Nonnemacher

  2. Center for Molecular Virology and Translational Neuroscience, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, 245 N. 15th St., Philadelphia, PA, 19102, USA

    Anupam Banerjee, Marianne Strazza, Brian Wigdahl, Vanessa Pirrone, Olimpia Meucci & Michael R. Nonnemacher

  3. Center for Neuroimmunology and CNS Therapeutics, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, 245 N. 15th St., Philadelphia, PA, 19102, USA

    Anupam Banerjee, Marianne Strazza, Brian Wigdahl, Vanessa Pirrone, Olimpia Meucci & Michael R. Nonnemacher

Authors
  1. Anupam Banerjee
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marianne Strazza
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Brian Wigdahl
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Vanessa Pirrone
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Olimpia Meucci
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Michael R. Nonnemacher
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Michael R. Nonnemacher.

Additional information

Anupam Banerjee and Marianne Strazza contributed equally to the manuscript.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Banerjee, A., Strazza, M., Wigdahl, B. et al. Role of mu-opioids as cofactors in human immunodeficiency virus type 1 disease progression and neuropathogenesis. J. Neurovirol. 17, 291–302 (2011). https://doi.org/10.1007/s13365-011-0037-2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13365-011-0037-2

Keywords

Search

Navigation