title: HIV-1 TAT inhibits microglial phagocytosis of Abeta peptide.
abstract: Human immunodeficiency virus (HIV)-associated dementia (HAD) is a subcortical neuropsychiatric syndrome that has increased in prevalence in the era of highly active antiretroviral therapy (HAART). Several studies demonstrated increased amyloidosis in brains of HIV patients and suggested that there may be a significant number of long-term HIV survivors with co-morbid Alzheimer's disease (AD) in the future. We show HIV-1 Tat protein inhibits microglial uptake of Abeta1-42 peptide, a process that is enhanced by interferon-gamma (IFN-gamma) and rescued by the STAT1 inhibitor (-)-epigallocatechin-3-gallate (EGCG). It is hypothesized that reduced Abeta uptake occurs through IFN-gamma mediated STAT1 activation. This process promotes a switch from a phagocytic to an antigen presenting phenotype in microglia through activation of class II transactivator (CIITA). Additionally, we show that HIV-1 Tat significantly disrupts apolipoprotein-3 (Apo-E3) promoted microglial Abeta uptake. As Tat has been shown to directly interact with the low density lipoprotein (LRP) receptor and thus inhibit the uptake of its ligands including apolipoprotein E4 (Apo-E4) and Abeta peptide in neurons, we further hypothesize that a similar inhibition of LRP may occur in microglia. Future studies will be required to fully characterize the mechanisms underlying IFN-gamma enhancement of HIV-1 Tats disruption of microglial phagocytosis of Abeta and Apo-E3.
authors.affiliation: Psychoimmunology Laboratory, Institute for Research in Psychiatry and Department of Psychiatry and Behavioral Medicine, University of South Florida College of Medicine Tampa, FL 33613, USA. bgiunta@health.usf.edu
authors.forename: Brian
authors.initials: B
authors.lastname: Giunta
authors.forename: Yuyan
authors.initials: Y
authors.lastname: Zhou
authors.forename: Huayan
authors.initials: H
authors.lastname: Hou
authors.forename: Elona
authors.initials: E
authors.lastname: Rrapo
authors.forename: Francisco
authors.initials: F
authors.lastname: Fernandez
authors.forename: Jun
authors.initials: J
authors.lastname: Tan
references.citation: J Virol. 1991 Feb;65(2):961-7
references.pmid: 1898974
references.citation: J Biol Chem. 1994 Jan 28;269(4):2764-72
references.pmid: 8300609
references.citation: J Virol. 1993 Jan;67(1):277-87
references.pmid: 8416373
references.citation: Biochem Biophys Res Commun. 1993 Apr 30;192(2):359-65
references.pmid: 8484748
references.citation: J Neuroimmunol. 1988 Jan;17(2):89-101
references.pmid: 2826540
references.citation: Genes Dev. 2000 May 1;14(9):1156-66
references.pmid: 10809673
references.citation: Arch Biochem Biophys. 1995 Jun 20;320(1):84-95
references.pmid: 7793988
references.citation: Brain Res Bull. 2004 Aug 30;64(2):165-70
references.pmid: 15342104
references.citation: Proc Natl Acad Sci U S A. 2007 Feb 13;104(7):2507-12
references.pmid: 17264212
references.citation: Glia. 2006 Aug 1;54(2):81-93
references.pmid: 16705672
references.citation: J Immunol. 1998 May 15;160(10):4671-80
references.pmid: 9590212
references.citation: Eur J Immunol. 2004 Jun;34(6):1513-25
references.pmid: 15162420
references.citation: Folia Neuropathol. 2000;38(4):175-82
references.pmid: 11693722
references.citation: Food Chem Toxicol. 2006 May;44(5):626-35
references.pmid: 16364532
references.citation: J Biol Chem. 1999 Nov 5;274(45):32301-8
references.pmid: 10542270
references.citation: Brain Res. 1993 Nov 12;627(2):199-204
references.pmid: 8298962
references.citation: AIDS Read. 2002 Aug;12(8):358-68
references.pmid: 12229893
references.citation: Neurology. 1993 Nov;43(11):2245-52
references.pmid: 8232937
references.citation: Nat Immunol. 2004 Sep;5(9):899-908
references.pmid: 15322541
references.citation: J Neurovirol. 2005;11 Suppl 3:16-22
references.pmid: 16540449
references.citation: Cell. 1993 Oct 8;75(1):135-46
references.pmid: 8402893
references.citation: J Biol Chem. 1996 Nov 22;271(47):30121-5
references.pmid: 8939961
references.citation: J Biol Chem. 1999 Oct 22;274(43):30631-5
references.pmid: 10521448
references.citation: Neurology. 2005 Aug 23;65(4):545-51
references.pmid: 16116114
references.citation: J Immunol. 1997 Aug 1;159(3):1344-51
references.pmid: 9233631
references.citation: Eur J Immunol. 2005 Mar;35(3):901-10
references.pmid: 15688347
references.citation: Brain Res. 2006 Dec 6;1123(1):216-225
references.pmid: 17078933
references.citation: Med Hypotheses. 2007;69(5):1140-3
references.pmid: 17433562
references.citation: Nat Med. 2001 May;7(5):612-8
references.pmid: 11329064
references.citation: J Neuroinflammation. 2006 Jul 21;3:16
references.pmid: 16859542
references.citation: J Neuropathol Exp Neurol. 1994 May;53(3):231-8
references.pmid: 8176406
references.citation: Biochem Biophys Res Commun. 2007 Mar 23;354(4):1004-9
references.pmid: 17270146
references.citation: Am J Pathol. 2003 May;162(5):1693-707
references.pmid: 12707054
references.citation: Food Chem Toxicol. 2006 May;44(5):636-50
references.pmid: 16387402
references.citation: Curr Pharm Des. 2006;12(9):1023-44
references.pmid: 16515484
references.citation: Curr Opin Cell Biol. 1994 Apr;6(2):253-9
references.pmid: 8024817
references.citation: Trends Neurosci. 1996 Aug;19(8):312-8
references.pmid: 8843599
references.citation: Nat Med. 2000 Aug;6(8):916-9
references.pmid: 10932230
references.citation: J Biol Chem. 1994 Sep 23;269(38):23403-6
references.pmid: 8089103
references.citation: Int J Dev Neurosci. 2006 Apr-May;24(2-3):167-76
references.pmid: 16472958
references.citation: Curr HIV Res. 2006 Jan;4(1):79-85
references.pmid: 16454713
references.citation: Neurotox Res. 2005 Oct;8(1-2):3-24
references.pmid: 16260383
references.citation: Nucleic Acids Res. 2002 Oct 1;30(19):4186-98
references.pmid: 12364597
references.citation: Neurobiol Dis. 2007 Apr;26(1):153-64
references.pmid: 17240154
references.citation: Nat Med. 2000 Dec;6(12):1380-7
references.pmid: 11100124
references.citation: Curr Infect Dis Rep. 2003 Jun;5(3):266-276
references.pmid: 12760825
references.citation: J Biol Chem. 2002 Aug 16;277(33):29889-96
references.pmid: 12032144
references.citation: J Neurovirol. 1999 Aug;5(4):327-41
references.pmid: 10463855
references.citation: J Neuroimmunol. 2002 Sep;130(1-2):1-9
references.pmid: 12225883
references.citation: J Neurol Sci. 2002 Oct 15;202(1-2):13-23
references.pmid: 12220687
references.citation: Clin Infect Dis. 1992 Jan;14(1):189-91
references.pmid: 1571427
references.citation: J Acquir Immune Defic Syndr. 2002 Oct 1;31 Suppl 2:S43-54
references.pmid: 12394782
references.citation: Proc Natl Acad Sci U S A. 1995 Oct 10;92(21):9480-4
references.pmid: 7568158
references.citation: Invest Ophthalmol Vis Sci. 2003 Jul;44(7):3083-93
references.pmid: 12824255
references.citation: J Neurovirol. 2002 Apr;8(2):136-42
references.pmid: 11935465
references.citation: Neurotox Res. 2005 Oct;8(1-2):51-61
references.pmid: 16260385
references.citation: Eur J Clin Invest. 2000 Jun;30(6):526-35
references.pmid: 10849022
references.citation: J Neurovirol. 2006 Jun;12(3):153-60
references.pmid: 16877296
references.citation: Nat Rev Immunol. 2005 Oct;5(10):793-806
references.pmid: 16200082
references.citation: J Gen Virol. 1993 Dec;74 ( Pt 12):2587-94
references.pmid: 8277265
references.citation: J Neurochem. 1999 Oct;73(4):1393-8
references.pmid: 10501182
references.citation: J Biol Chem. 2001 Feb 2;276(5):3254-61
references.pmid: 11024024
references.citation: J Biol Chem. 1995 Aug 4;270(31):18666-71
references.pmid: 7629198
references.citation: Neurology. 1995 Feb;45(2):367-73
references.pmid: 7854540
references.citation: Nat Med. 1998 Oct;4(10):1182-4
references.pmid: 9771753
references.citation: Curr Med Chem. 2005;12(16):1819-28
references.pmid: 16101503
references.citation: Mol Cell Biol. 2000 Oct;20(19):7273-81
references.pmid: 10982844
references.citation: Exp Dermatol. 2006 Jun;15(6):441-6
references.pmid: 16689860
references.citation: Mol Cell Biol. 1999 Jan;19(1):431-40
references.pmid: 9858567
references.citation: EMBO J. 1997 May 15;16(10):2851-60
references.pmid: 9184229
references.citation: Nat Neurosci. 2002 Dec;5(12):1288-93
references.pmid: 12402041
references.citation: Mol Cell Biol. 2001 Aug;21(15):4919-28
references.pmid: 11438649
references.citation: Science. 1994 May 6;264(5160):850-2
references.pmid: 8171342
references.citation: J Biol Chem. 1995 Aug 25;270(34):19791-9
references.pmid: 7649988
references.citation: Am J Prev Med. 1986 Sep-Oct;2(5):297-305
references.pmid: 3330954
references.citation: J Biol Chem. 2002 Mar 29;277(13):11292-6
references.pmid: 11792705
references.citation: J Biol Chem. 1993 May 15;268(14):10160-7
references.pmid: 7683668
references.citation: Biochemistry. 1997 Aug 26;36(34):10571-80
references.pmid: 9265639
references.citation: Front Biosci. 2004 May 01;9:1073-81
references.pmid: 14977530
references.citation: Cell Mol Biol (Noisy-le-grand). 2002 Mar;48(2):137-50
references.pmid: 11995633
references.citation: Glia. 2002 Nov;40(2):260-9
references.pmid: 12379913
references.citation: Am J Physiol Gastrointest Liver Physiol. 2004 Nov;287(5):G954-61
references.pmid: 15231486
references.citation: J Neurosci. 2006 May 10;26(19):5143-52
references.pmid: 16687505
references.citation: AIDS. 1997 Oct;11(12):1421-31
references.pmid: 9342064
references.citation: Neuron. 1996 Sep;17(3):553-65
references.pmid: 8816718
references.citation: J Neurosci. 2003 Sep 10;23(23):8417-22
references.pmid: 12968004
references.citation: J Neurol Neurosurg Psychiatry. 1998 Jul;65(1):29-33
references.pmid: 9667557
references.citation: Exp Neurol. 1998 Dec;154(2):276-88
references.pmid: 9878167
references.citation: J Biol Chem. 2006 Jun 16;281(24):16419-27
references.pmid: 16624814
references.citation: EMBO J. 1996 Oct 15;15(20):5616-26
references.pmid: 8896455
references.citation: Curr HIV/AIDS Rep. 2004 Sep;1(3):122-7
references.pmid: 16091232
references.citation: J Neurovirol. 2004 Aug;10(4):223-32
references.pmid: 15371152
references.citation: Cell. 1994 Mar 11;76(5):821-8
references.pmid: 7510216
references.citation: Curr Opin Lipidol. 1995 Apr;6(2):86-91
references.pmid: 7773573
references.citation: Brain Res. 1993 Jan 22;601(1-2):154-63
references.pmid: 8431762
references.citation: AIDS. 2005 Mar 4;19(4):407-11
references.pmid: 15750394
references.citation: J Immunol. 2007 Mar 1;178(5):3226-36
references.pmid: 17312171
references.citation: AIDS. 2005 Jan 28;19(2):127-35
references.pmid: 15668537
references.citation: J Acquir Immune Defic Syndr. 2002 Oct 1;31(2):171-7
references.pmid: 12394795
references.citation: AIDS. 1992 Sep;6(9):915-23
references.pmid: 1326996
references.citation: J Biol Chem. 2000 Nov 24;275(47):37224-31
references.pmid: 10978311
references.citation: J Cereb Blood Flow Metab. 2002 Nov;22(11):1311-8
references.pmid: 12439288
references.citation: J Leukoc Biol. 2004 Aug;76(2):451-61
references.pmid: 15136588
references.citation: Neuroscience. 1999;90(4):1217-26
references.pmid: 10338292
references.citation: Neurology. 2004 Dec 28;63(12):2436-8
references.pmid: 15623723
references.citation: Trends Immunol. 2002 Feb;23(2):96-101
references.pmid: 11929133
references.citation: J Am Geriatr Soc. 2005 Jul;53(7):1101-7
references.pmid: 16108925
references.citation: J Virol. 1992 Jul;66(7):4228-32
references.pmid: 1602543
references.citation: J Neuroimmunol. 2003 Nov;144(1-2):68-79
references.pmid: 14597100
references.citation: J Neurochem. 1993 Dec;61(6):2147-54
references.pmid: 8245966
references.citation: Neurochem Int. 2001 Nov-Dec;39(5-6):333-40
references.pmid: 11578768
references.citation: Neurology. 2005 Nov 8;65(9):1490-2
references.pmid: 16275845
references.citation: AIDS Res Hum Retroviruses. 1993 Jul;9(7):677-85
references.pmid: 8369172
references.citation: J Immunol. 1999 Feb 1;162(3):1384-91
references.pmid: 9973393
references.citation: Cell Death Differ. 2005 Aug;12 Suppl 1:893-904
references.pmid: 15761472
references.citation: J Neuropathol Exp Neurol. 2002 Jan;61(1):85-90
references.pmid: 11829347
references.citation: Acta Neuropathol. 1992;84(3):225-33
references.pmid: 1414275
references.citation: Arteriosclerosis. 1988 Jan-Feb;8(1):1-21
references.pmid: 3277611
references.citation: Mol Cell Biol. 2002 Jul;22(13):4781-91
references.pmid: 12052885
references.citation: AIDS. 2005 Jan 28;19(2):203-4
references.pmid: 15668546
references.citation: Int J Vitam Nutr Res. 2004 Jul;74(4):269-78
references.pmid: 15580809
references.citation: J Biol Chem. 1995 Nov 10;270(45):27063-71
references.pmid: 7592957
references.citation: J Leukoc Biol. 2000 Sep;68(3):413-22
references.pmid: 10985259
references.citation: Biochem J. 1995 Mar 1;306 ( Pt 2):599-604
references.pmid: 7534068
references.citation: J Mol Neurosci. 2004;23(3):235-46
references.pmid: 15181252
references.citation: Glia. 1993 Jan;7(1):75-83
references.pmid: 8423065
references.citation: J Leukoc Biol. 2003 Mar;73(3):407-16
references.pmid: 12629155