Skip to main content

Advertisement

SpringerLink
Log in

Extracellular HIV-1 viral protein R affects astrocytic glyceraldehyde 3-phosphate dehydrogenase activity and neuronal survival

  • Published:
Journal of NeuroVirology Aims and scope Submit manuscript

Abstract

Extracellular human immunodeficiency virus type 1 (HIV-1) viral protein R (Vpr) is a pleiotropic protein accomplishing several functions within the viral life cycle. While Vpr has been described extensively as an intracellular protein, very little is known about its role as an extracellular protein. In fact, HIV-1 Vpr has been detected in the blood, serum, and cerebrospinal fluid of HIV-1-infected patients, with concentrations increasingly higher in late-stage disease. To determine the role exogenous Vpr plays in HIV-associated central nervous system dysfunction, primary human fetal astrocytes were exposed to recombinant Vpr and a time- and dose-dependent decrease was demonstrated in two fundamental intracellular metabolites (adenosine-5′-triphosphate (ATP) and glutathione (GSH)). Additionally, exposure to exogenous Vpr led to increased caspase activity and secretion of proinflammatory cytokines IL-6 and IL-8 and chemoattractants, monocyte chemotactic protein-1, and migration inhibition factor. Extracellular Vpr also dampened the glycolytic pathway through impairment of glyceraldehyde 3-phosphate dehydrogenase activity, causing a decline in the levels of ATP. The reduction in intracellular ATP increased reactive oxygen species buildup, decreasing GSH concentrations, which affected several genes in the oxidative stress pathway. In addition, exposure of the SK-N-SH neuroblastoma cell line to conditioned medium from exogenous Vpr-treated astrocytes decreased synthesis of GSH, leading to their apoptosis. These observations point to a role that Vpr plays in altering astrocytic metabolism and indirectly affecting neuronal survival. We propose a model that may explain some of the neurological damage and therefore neurocognitive impairment observed during the course of HIV-1 disease.

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
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Abbreviations

OS:

Oxidative stress

ROS:

Reactive oxygen species

GSH:

Glutathione

GSSG:

Oxidized glutathione

Vpr:

Viral protein R

NAC:

N-acetyl-l-cysteine

ANT:

Adenine nucleotide translocator

MCP-1:

Monocyte chemotactic protein-1

MIF:

Migration inhibitor factor

PAI-1:

Plasminogen activator inhibitor-1

BSO:

Buthionine sulfoximine

GST:

Glutathione S-transferase

HA:

Hemagglutinin

CPT:

Camptothecin

qRT-PCR:

Quantitative real-time PCR

HFA:

Human fetal astrocytes

GFAP:

Glial fibrillary acidic protein

SCARA3:

Scavenger receptor class A member 3

rVpr:

Recombinant Vpr

DGK:

Diacylglycerol kinase

BBB:

Blood–brain barrier

References

  • Acharjee S, Noorbakhsh F, Stemkowski PL, Olechowski C, Cohen EA, Ballanyi K, Kerr B, Pardo C, Smith PA, Power C (2010) HIV-1 viral protein R causes peripheral nervous system injury associated with in vivo neuropathic pain. FASEB J Off Publ Fed Am Soc Exp Biol 24:4343–4353

    CAS  Google Scholar 

  • Agrawal L, Louboutin JP, Marusich E, Reyes BA, Van Bockstaele EJ, Strayer DS (2010) Dopaminergic neurotoxicity of HIV-1 gp120: reactive oxygen species as signaling intermediates. Brain Res 1306:116–130

    Article  CAS  Google Scholar 

  • Baruchel S, Wainberg MA (1992) The role of oxidative stress in disease progression in individuals infected by the human immunodeficiency virus. J Leukoc Biol 52:111–114

    CAS  Google Scholar 

  • Brookes PS, Yoon Y, Robotham JL, Anders MW, Sheu SS (2004) Calcium, ATP, and ROS: a mitochondrial love–hate triangle. Am J Physiol Cell Physiol 287:C817–C833

    Article  CAS  Google Scholar 

  • Chabory E, Damon C, Lenoir A, Henry-Berger J, Vernet P, Cadet R, Saez F, Drevet JR (2010) Mammalian glutathione peroxidases control acquisition and maintenance of spermatozoa integrity. J Anim Sci 88:1321–1331

    Article  CAS  Google Scholar 

  • Cheng X, Mukhtar M, Acheampong EA, Srinivasan A, Rafi M, Pomerantz RJ, Parveen Z (2007) HIV-1 Vpr potently induces programmed cell death in the CNS in vivo. DNA Cell Biol 26:116–131

    Article  CAS  Google Scholar 

  • Connor RI, Chen BK, Choe S, Landau NR (1995) Vpr is required for efficient replication of human immunodeficiency virus type-1 in mononuclear phagocytes. Virology 206:935–944

    Article  CAS  Google Scholar 

  • Cui J, Tungaturthi PK, Ayyavoo V, Ghafouri M, Ariga H, Khalili K, Srinivasan A, Amini S, Sawaya BE (2006) The role of Vpr in the regulation of HIV-1 gene expression. Cell Cycle 5:2626–2638

    Article  CAS  Google Scholar 

  • Cutler RG, Haughey NJ, Tammara A, McArthur JC, Nath A, Reid R, Vargas DL, Pardo CA, Mattson MP (2004) Dysregulation of sphingolipid and sterol metabolism by ApoE4 in HIV dementia. Neurology 63:626–630

    Article  CAS  Google Scholar 

  • Cysique LA, Vaida F, Letendre S, Gibson S, Cherner M, Woods SP, McCutchan JA, Heaton RK, Ellis RJ (2009) Dynamics of cognitive change in impaired HIV-positive patients initiating antiretroviral therapy. Neurology 73:342–348

    Article  CAS  Google Scholar 

  • Dastoor Z, Dreyer JL (2001) Potential role of nuclear translocation of glyceraldehyde-3-phosphate dehydrogenase in apoptosis and oxidative stress. J Cell Sci 114:1643–1653

    CAS  Google Scholar 

  • Deshmane SL, Mukerjee R, Fan S, Del Valle L, Michiels C, Sweet T, Rom I, Khalili K, Rappaport J, Amini S, Sawaya BE (2009) Activation of the oxidative stress pathway by HIV-1 Vpr leads to induction of hypoxia-inducible factor 1alpha expression. J Biol Chem 284:11364–11373

    Article  CAS  Google Scholar 

  • Ferrucci A, Nonnemacher MR, Cohen EA, Wigdahl B (2012) Extracellular human immunodeficiency virus type 1 viral protein R causes reductions in astrocytic ATP and glutathione levels compromising the antioxidant reservoir. Virus Res 167:358–369

    Article  CAS  Google Scholar 

  • Garg SK, Banerjee R, Kipnis J (2008) Neuroprotective immunity: T cell-derived glutamate endows astrocytes with a neuroprotective phenotype. J Immunol 180:3866–3873

    CAS  Google Scholar 

  • Gincel D, Zaid H, Shoshan-Barmatz V (2001) Calcium binding and translocation by the voltage-dependent anion channel: a possible regulatory mechanism in mitochondrial function. Biochem J 358:147–155

    Article  CAS  Google Scholar 

  • Greiner VJ, Shvadchak V, Fritz J, Arntz Y, Didier P, Frisch B, Boudier C, Mely Y, de Rocquigny H (2011) Characterization of the mechanisms of HIV-1 Vpr(52–96) internalization in cells. Biochimie 93:1647–1658

    Article  CAS  Google Scholar 

  • Halestrap AP (2009) What is the mitochondrial permeability transition pore? J Mol Cell Cardiol 46:821–831

    Article  CAS  Google Scholar 

  • Halestrap AP, Woodfield KY, Connern CP (1997) Oxidative stress, thiol reagents, and membrane potential modulate the mitochondrial permeability transition by affecting nucleotide binding to the adenine nucleotide translocase. J Biol Chem 272:3346–3354

    Article  CAS  Google Scholar 

  • He J, Choe S, Walker R, Di Marzio P, Morgan DO, Landau NR (1995) Human immunodeficiency virus type 1 viral protein R (Vpr) arrests cells in the G2 phase of the cell cycle by inhibiting p34cdc2 activity. J Virol 69:6705–6711

    CAS  Google Scholar 

  • Herzenberg LA, De Rosa SC, Dubs JG, Roederer M, Anderson MT, Ela SW, Deresinski SC (1997) Glutathione deficiency is associated with impaired survival in HIV disease. Proc Natl Acad Sci U S A 94:1967–1972

    Article  CAS  Google Scholar 

  • Hino H, Akiyama H, Iseki E, Kato M, Kondo H, Ikeda K, Kosaka K (2001) Immunohistochemical localization of plasminogen activator inhibitor-1 in rat and human brain tissues. Neurosci Lett 297:105–108

    Article  CAS  Google Scholar 

  • Hoshino S, Konishi M, Mori M, Shimura M, Nishitani C, Kuroki Y, Koyanagi Y, Kano S, Itabe H, Ishizaka Y (2010) HIV-1 Vpr induces TLR4/MyD88-mediated IL-6 production and reactivates viral production from latency. J Leukoc Biol 87:1133–1143

    Article  CAS  Google Scholar 

  • Hoshino S, Sun B, Konishi M, Shimura M, Segawa T, Hagiwara Y, Koyanagi Y, Iwamoto A, Mimaya J, Terunuma H, Kano S, Ishizaka Y (2007) Vpr in plasma of HIV type 1-positive patients is correlated with the HIV type 1 RNA titers. AIDS Res Hum Retroviruses 23:391–397

    Article  CAS  Google Scholar 

  • Jacotot E, Ferri KF, El Hamel C, Brenner C, Druillennec S, Hoebeke J, Rustin P, Metivier D, Lenoir C, Geuskens M, Vieira HL, Loeffler M, Belzacq AS, Briand JP, Zamzami N, Edelman L, Xie ZH, Reed JC, Roques BP, Kroemer G (2001) Control of mitochondrial membrane permeabilization by adenine nucleotide translocator interacting with HIV-1 viral protein rR and Bcl-2. J Exp Med 193:509–519

    Article  CAS  Google Scholar 

  • Jacotot E, Ravagnan L, Loeffler M, Ferri KF, Vieira HL, Zamzami N, Costantini P, Druillennec S, Hoebeke J, Briand JP, Irinopoulou T, Daugas E, Susin SA, Cointe D, Xie ZH, Reed JC, Roques BP, Kroemer G (2000) The HIV-1 viral protein R induces apoptosis via a direct effect on the mitochondrial permeability transition pore. J Exp Med 191:33–46

    Article  CAS  Google Scholar 

  • Jones GJ, Barsby NL, Cohen EA, Holden J, Harris K, Dickie P, Jhamandas J, Power C (2007) HIV-1 Vpr causes neuronal apoptosis and in vivo neurodegeneration. J Neurosci 27:3703–3711

    Article  CAS  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 82:2528–2542

    Article  CAS  Google Scholar 

  • Klegeris A, Walker DG, McGeer PL (1997) Regulation of glutamate in cultures of human monocytic THP-1 and astrocytoma U-373 MG cells. J Neuroimmunol 78:152–161

    Article  CAS  Google Scholar 

  • Krasowska-Zoladek A, Banaszewska M, Kraszpulski M, Konat GW (2007) Kinetics of inflammatory response of astrocytes induced by TLR 3 and TLR4 ligation. J Neurosci Res 85:205–212

    Article  CAS  Google Scholar 

  • Lassiter C, Fan X, Joshi PC, Jacob BA, Sutliff RL, Jones DP, Koval M, Guidot DM (2009) HIV-1 transgene expression in rats causes oxidant stress and alveolar epithelial barrier dysfunction. AIDS Res Ther 6:1

    Article  Google Scholar 

  • Levy DN, Refaeli Y, MacGregor RR, Weiner DB (1994) Serum Vpr regulates productive infection and latency of human immunodeficiency virus type 1. Proc Natl Acad Sci U S A 91:10873–10877

    Article  CAS  Google Scholar 

  • Levy DN, Refaeli Y, Weiner DB (1995) Extracellular Vpr protein increases cellular permissiveness to human immunodeficiency virus replication and reactivates virus from latency. J Virol 69:1243–1252

    CAS  Google Scholar 

  • Li J, Bentsman G, Potash MJ, Volsky DJ (2007) Human immunodeficiency virus type 1 efficiently binds to human fetal astrocytes and induces neuroinflammatory responses independent of infection. BMC Neurosci 8:31

    Article  Google Scholar 

  • Lipton SA (1994) AIDS-related dementia and calcium homeostasis. Ann N Y Acad Sci 747:205–224

    Article  CAS  Google Scholar 

  • Liu X, Jana M, Dasgupta S, Koka S, He J, Wood C, Pahan K (2002) Human immunodeficiency virus type 1 (HIV-1) tat induces nitric-oxide synthase in human astroglia. J Biol Chem 277:39312–39319

    Article  CAS  Google Scholar 

  • Liu Y, Liu W, Song XD, Zuo J (2005) Effect of GRP75/mthsp70/PBP74/mortalin overexpression on intracellular ATP level, mitochondrial membrane potential and ROS accumulation following glucose deprivation in PC12 cells. Mol Cell Biochem 268:45–51

    Article  CAS  Google Scholar 

  • Ma J, Yee A, Brewer HB Jr, Das S, Potter H (1994) Amyloid-associated proteins alpha 1-antichymotrypsin and apolipoprotein E promote assembly of Alzheimer beta-protein into filaments. Nature 372:92–94

    Article  CAS  Google Scholar 

  • Macreadie IG, Arunagiri CK, Hewish DR, White JF, Azad AA (1996) Extracellular addition of a domain of HIV-1 Vpr containing the amino acid sequence motif H(S/F)RIG causes cell membrane permeabilization and death. Mol Microbiol 19:1185–1192

    Article  CAS  Google Scholar 

  • Maingat F, Halloran B, Acharjee S, van Marle G, Church D, Gill MJ, Uwiera RR, Cohen EA, Meddings J, Madsen K, Power C (2011) Inflammation and epithelial cell injury in AIDS enteropathy: involvement of endoplasmic reticulum stress. FASEB J: Off Publ Fed Am Soc Exp Biol 25:2211–2220

    CAS  Google Scholar 

  • McArthur JC (2004) HIV dementia: an evolving disease. J Neuroimmunol 157:3–10

    Article  CAS  Google Scholar 

  • Muratori C, Mangino G, Affabris E, Federico M (2010) Astrocytes contacting HIV-1-infected macrophages increase the release of CCL2 in response to the HIV-1-dependent enhancement of membrane-associated TNFalpha in macrophages. Glia 58:1893–1904

    Article  Google Scholar 

  • Muthumani K, Kudchodkar S, Papasavvas E, Montaner LJ, Weiner DB, Ayyavoo V (2000) HIV-1 Vpr regulates expression of beta chemokines in human primary lymphocytes and macrophages. J Leukoc Biol 68:366–372

    CAS  Google Scholar 

  • Nath A, Schiess N, Venkatesan A, Rumbaugh J, Sacktor N, McArthur J (2008) Evolution of HIV dementia with HIV infection. Int Rev Psychiatry 20:25–31

    Article  Google Scholar 

  • Noorbakhsh F, Ramachandran R, Barsby N, Ellestad KK, LeBlanc A, Dickie P, Baker G, Hollenberg MD, Cohen EA, Power C (2010) MicroRNA profiling reveals new aspects of HIV neurodegeneration: caspase-6 regulates astrocyte survival. FASEB J 24:1799–1812

    Article  CAS  Google Scholar 

  • Pebay-Peyroula E, Dahout-Gonzalez C, Kahn R, Trezeguet V, Lauquin GJ, Brandolin G (2003) Structure of mitochondrial ADP/ATP carrier in complex with carboxyatractyloside. Nature 426:39–44

    Article  CAS  Google Scholar 

  • Pellerin L, Magistretti PJ (1994) Glutamate uptake into astrocytes stimulates aerobic glycolysis: a mechanism coupling neuronal activity to glucose utilization. Proc Natl Acad Sci U S A 91:10625–10629

    Article  CAS  Google Scholar 

  • Perl A, Banki K (2000) Genetic and metabolic control of the mitochondrial transmembrane potential and reactive oxygen intermediate production in HIV disease. Antioxid Redox Signal 2:551–573

    Article  CAS  Google Scholar 

  • Piller SC, Ewart GD, Premkumar A, Cox GB, Gage PW (1996) Vpr protein of human immunodeficiency virus type 1 forms cation-selective channels in planar lipid bilayers. Proc Natl Acad Sci U S A 93:111–115

    Article  CAS  Google Scholar 

  • Piller SC, Jans P, Gage PW, Jans DA (1998) Extracellular HIV-1 virus protein R causes a large inward current and cell death in cultured hippocampal neurons: implications for AIDS pathology. Proc Natl Acad Sci U S A 95:4595–4600

    Article  CAS  Google Scholar 

  • Pollicita M, Muscoli C, Sgura A, Biasin A, Granato T, Masuelli L, Mollace V, Tanzarella C, Del Duca C, Rodino P, Perno CF, Aquaro S (2009) Apoptosis and telomeres shortening related to HIV-1 induced oxidative stress in an astrocytoma cell line. BMC Neurosci 10:51

    Article  Google Scholar 

  • Popa C, van Lieshout AW, Roelofs MF, Geurts-Moespot A, van Riel PL, Calandra T, Sweep FC, Radstake TR (2006) MIF production by dendritic cells is differentially regulated by Toll-like receptors and increased during rheumatoid arthritis. Cytokine 36:51–56

    Article  CAS  Google Scholar 

  • Potter SJ, Lemey P, Achaz G, Chew CB, Vandamme AM, Dwyer DE, Saksena NK (2004) HIV-1 compartmentalization in diverse leukocyte populations during antiretroviral therapy. J Leukoc Biol 76:562–570

    Article  CAS  Google Scholar 

  • Regis EG, Barreto-de-Souza V, Morgado MG, Bozza MT, Leng L, Bucala R, Bou-Habib DC (2010) Elevated levels of macrophage migration inhibitory factor (MIF) in the plasma of HIV-1-infected patients and in HIV-1-infected cell cultures: a relevant role on viral replication. Virology 399:31–38

    Article  CAS  Google Scholar 

  • Roger T, Froidevaux C, Martin C, Calandra T (2003) Macrophage migration inhibitory factor (MIF) regulates host responses to endotoxin through modulation of Toll-like receptor 4 (TLR4). J Endotoxin Res 9:119–123

    CAS  Google Scholar 

  • Rom I, Deshmane SL, Mukerjee R, Khalili K, Amini S, Sawaya BE (2009) HIV-1 Vpr deregulates calcium secretion in neural cells. Brain Res 1275:81–86

    Article  CAS  Google Scholar 

  • Sabbah EN, Druillennec S, Morellet N, Bouaziz S, Kroemer G, Roques BP (2006) Interaction between the HIV-1 protein Vpr and the adenine nucleotide translocator. Chem Biol Drug Des 67:145–154

    Article  CAS  Google Scholar 

  • Sabbah EN, Roques BP (2005) Critical implication of the (70–96) domain of human immunodeficiency virus type 1 Vpr protein in apoptosis of primary rat cortical and striatal neurons. J Neurovirol 11:489–502

    Article  CAS  Google Scholar 

  • Sen N, Hara MR, Kornberg MD, Cascio MB, Bae BI, Shahani N, Thomas B, Dawson TM, Dawson VL, Snyder SH, Sawa A (2008) Nitric oxide-induced nuclear GAPDH activates p300/CBP and mediates apoptosis. Nat Cell Biol 10:866–873

    Article  CAS  Google Scholar 

  • Sherman MP, Schubert U, Williams SA, de Noronha CM, Kreisberg JF, Henklein P, Greene WC (2002) HIV-1 Vpr displays natural protein-transducing properties: implications for viral pathogenesis. Virology 302:95–105

    Article  CAS  Google Scholar 

  • Shinya E, Owaki A, Shimizu M, Takeuchi J, Kawashima T, Hidaka C, Satomi M, Watari E, Sugita M, Takahashi H (2004) Endogenously expressed HIV-1 nef down-regulates antigen-presenting molecules, not only class I MHC but also CD1a, in immature dendritic cells. Virology 326:79–89

    Article  CAS  Google Scholar 

  • Sorg O, Horn TF, Yu N, Gruol DL, Bloom FE (1997) Inhibition of astrocyte glutamate uptake by reactive oxygen species: role of antioxidant enzymes. Mol Med 3:431–440

    CAS  Google Scholar 

  • Strazza M, Pirrone V, Wigdahl B, Nonnemacher MR (2011) Breaking down the barrier: the effects of HIV-1 on the blood–brain barrier. Brain Res 1399:96–115

    Article  CAS  Google Scholar 

  • Sukhanov S, Higashi Y, Shai SY, Itabe H, Ono K, Parthasarathy S, Delafontaine P (2006) Novel effect of oxidized low-density lipoprotein: cellular ATP depletion via downregulation of glyceraldehyde-3-phosphate dehydrogenase. Circ Res 99:191–200

    Article  CAS  Google Scholar 

  • Thangima Zannat M, Bhattacharjee RB, Bag J (2011) In the absence of cellular poly (A) binding protein, the glycolytic enzyme GAPDH translocated to the cell nucleus and activated the GAPDH mediated apoptotic pathway by enhancing acetylation and serine 46 phosphorylation of p53. Biochem Biophys Res Commun 409:171–176

    Article  Google Scholar 

  • Tran ND, Schreiber SS, Fisher M (1998) Astrocyte regulation of endothelial tissue plasminogen activator in a blood–brain barrier model. J Cereb Blood Flow Metab: Off J Int Soc Cereb Blood Flow Metab 18:1316–1324

    Article  CAS  Google Scholar 

  • Treitinger A, Spada C, Ferreira LA, Neto MS, Reis M, Verdi JC, de Miranda AF, de Oliveira OV, Van der Sander SM, Abdalla DS (2000) Hepatitis B and hepatitis C prevalence among blood donors and HIV-1 infected patients in Florianopolis–Brazil. Braz J Infect Dis 4:192–196

    CAS  Google Scholar 

  • Trotti D, Rossi D, Gjesdal O, Levy LM, Racagni G, Danbolt NC, Volterra A (1996) Peroxynitrite inhibits glutamate transporter subtypes. J Biol Chem 271:5976–5979

    Article  CAS  Google Scholar 

  • Verity MA, Torres M, Sarafian T (1991) Paradoxical potentiation by low extracellular Ca2+ of acute chemical anoxic neuronal injury in cerebellar granule cell culture. Mol Chem Neuropathol 15:217–233, Sponsored by the International Society for Neurochemistry and the World Federation of Neurology and research groups on neurochemistry and cerebrospinal fluid

    Article  CAS  Google Scholar 

  • Vivithanaporn P, Maingat F, Lin LT, Na H, Richardson CD, Agrawal B, Cohen EA, Jhamandas JH, Power C (2010) Hepatitis C virus core protein induces neuroimmune activation and potentiates human immunodeficiency virus-1 neurotoxicity. PLoS One 5:e12856

    Article  Google Scholar 

  • Wolf MB, Baynes JW (2006) The anti-cancer drug, doxorubicin, causes oxidant stress-induced endothelial dysfunction. Biochim Biophys Acta 1760:267–271

    Article  CAS  Google Scholar 

  • Zhang HS, Li HY, Zhou Y, Wu MR, Zhou HS (2009) Nrf2 is involved in inhibiting Tat-induced HIV-1 long terminal repeat transactivation. Free Radic Biol Med 47:261–268

    Article  CAS  Google Scholar 

  • Zhou Y, Yau C, Gray JW, Chew K, Dairkee SH, Moore DH, Eppenberger U, Eppenberger-Castori S, Benz CC (2007) Enhanced NF kappa B and AP-1 transcriptional activity associated with antiestrogen resistant breast cancer. BMC Cancer 7:59

    Article  Google Scholar 

Download references

Acknowledgments

We would like to thank Drs. Nathaniel Landau (NIH AIDS Research Program) and Jeffrey Kopp (NIH, Kidney Disease Section) for providing the Vpr plasmid and the anti-Vpr antibody, respectively. We also thank Dr. Bassel Sawaya (Temple University, Philadelphia, PA, USA) for providing the GST-Vpr plasmid. This work 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 to BW] and the National Institute of Drug Abuse [DA19807 to BW]. Dr. Michael Nonnemacher was also supported by faculty development funds provided by the Department of Microbiology and Immunology and the Institute for Molecular Medicine and Infectious Disease.

Author information

Authors and Affiliations

  1. School of Biomedical Engineering, Science and Health Systems, Drexel University College of Medicine, Philadelphia, PA, 19102, USA

    Adriano Ferrucci

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

    Adriano Ferrucci, Michael R. Nonnemacher & Brian Wigdahl

  3. Department of Microbiology and Immunology, Drexel University College of Medicine, 2900 Queen Lane, Philadelphia, PA, 19129, USA

    Adriano Ferrucci, Michael R. Nonnemacher & Brian Wigdahl

Authors
  1. Adriano Ferrucci
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michael R. Nonnemacher
    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

Corresponding author

Correspondence to Brian Wigdahl.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ferrucci, A., Nonnemacher, M.R. & Wigdahl, B. Extracellular HIV-1 viral protein R affects astrocytic glyceraldehyde 3-phosphate dehydrogenase activity and neuronal survival. J. Neurovirol. 19, 239–253 (2013). https://doi.org/10.1007/s13365-013-0170-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13365-013-0170-1

Keywords

Search

Navigation