beta-Chemokine production by neural and glial progenitor cells is enhanced by HIV-1 Tat: effects on microglial migration.
Human immunodeficiency virus (HIV)-1 neuropathology results from collective effects of viral proteins and inflammatory mediators on several cell types. Significant damage is mediated indirectly through inflammatory conditions promulgated by glial cells, including microglia that are productively infected by HIV-1, and astroglia. Neural and glial progenitors exist in both developing and adult brains. To determine whether progenitors are targets of HIV-1, a multi-plex assay was performed to assess chemokine/cytokine expression after treatment with viral proteins transactivator of transcription (Tat) or glycoprotein 120 (gp120). In the initial screen, ten analytes were basally released by murine striatal progenitors. The beta-chemokines CCL5/regulated upon activation, normal T cell expressed and secreted, CCL3/macrophage inflammatory protein-1alpha, and CCL4/macrophage inflammatory protein-1beta were increased by 12-h exposure to HIV-1 Tat. Secreted factors from Tat-treated progenitors were chemoattractive towards microglia, an effect blocked by 2D7 anti-CCR5 antibody pre-treatment. Tat and opiates have interactive effects on astroglial chemokine secretion, but this interaction did not occur in progenitors. gp120 did not affect chemokine/cytokine release, although both CCR5 and CXCR4, which serve as gp120 co-receptors, were detected in progenitors. We postulate that chemokine production by progenitors may be a normal, adaptive process that encourages immune inspection of newly generated cells. Pathogens such as HIV might usurp this function to create a maladaptive state, especially during development or regeneration, when progenitors are numerous.
Hahn
Yun Kyung
YK
Department of Anatomy and Neurobiology, Virginia Commonwealth University, Richmond, Virginia 23298-0709, USA.
Vo
Phu
P
Fitting
Sylvia
S
Block
Michelle L
ML
Hauser
Kurt F
KF
Knapp
Pamela E
PE
D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D018925:Chemokines / Q000096:biosynthesis*; D002633:Chemotaxis; D003342:Corpus Striatum / Q000166:cytology / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis; D053595:Embryonic Stem Cells / Q000378:metabolism; D015699:HIV Envelope Protein gp120 / Q000378:metabolism; D015497:HIV-1 / Q000378:metabolism*; D051379:Mice; D009457:Neuroglia / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D053610:Opiate Alkaloids / Q000494:pharmacology; D013234:Stem Cells / Q000378:metabolism*; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000378:metabolism*
D018925:Chemokines; D016207:Cytokines; D015699:HIV Envelope Protein gp120; D053610:Opiate Alkaloids; C514793:gp120 protein, Human immunodeficiency virus 1; D054322:tat Gene Products, Human Immunodeficiency Virus
Glia. 2009 Jan 15;57(2):194-206
18756534
Nat Rev Neurosci. 2007 Jan;8(1):57-69
17180163
Pediatrics. 1997 Jul;100(1):E5
9200379
AIDS. 1995 Feb;9(2):137-43
7536422
Proc Natl Acad Sci U S A. 2003 Dec 23;100(26):15983-8
14668448
Cytokine Growth Factor Rev. 2002 Dec;13(6):455-81
12401480
Neuron. 2000 Nov;28(2):385-97
11144350
J Pharmacol Exp Ther. 1997 Jan;280(1):61-6
8996182
J Neurovirol. 2000 Apr;6(2):145-55
10822328
Proc Natl Acad Sci U S A. 1998 Mar 17;95(6):3117-21
9501225
Cytokine. 2005 Dec 21;32(6):270-9
16377203
Neurosci Lett. 2004 Oct 7;369(1):24-7
15380301
Blood. 2008 Dec 15;112(13):4991-8
18812467
Neurosci Lett. 1982 Apr 16;29(2):183-8
6178060
Dev Neurosci. 2004 Mar-Aug;26(2-4):148-65
15711057
J Neuroimmune Pharmacol. 2006 Jun;1(2):182-91
18040783
Cell. 1990 Feb 23;60(4):585-95
1689217
J Infect Dis. 1999 Aug;180(2):310-9
10395844
J Neuropathol Exp Neurol. 2001 Sep;60(9):885-92
11556545
J Leukoc Biol. 2005 Dec;78(6):1233-41
16314440
Proc Natl Acad Sci U S A. 1996 Jan 23;93(2):700-4
8570619
AIDS. 2004 Jan 1;18 Suppl 1:S69-74
15075500
Glia. 2006 Jul;54(1):1-10
16652341
Vaccine. 2008 Jun 6;26(24):3008-15
18243436
Front Biosci. 2008 Jan 01;13:1294-307
17981630
Science. 1995 Dec 15;270(5243):1811-5
8525373
J Cell Sci. 2006 Nov 1;119(Pt 21):4520-30
17046994
Eur J Neurosci. 2004 Jun;19(12):3171-82
15217373
Neurology. 1998 Jun;50(6):1814-20
9633733
Brain Pathol. 2003 Apr;13(2):144-54
12744468
J Neurosci. 2009 Jan 7;29(1):263-7
19129402
Curr HIV Res. 2006 Jul;4(3):319-27
16842084
Curr HIV Res. 2005 Jul;3(3):277-88
16022659
J Neurovirol. 1997 Aug;3(4):290-8
9291237
J Neuroimmunol. 2006 Sep;178(1-2):9-16
16831471
Glia. 2005 Apr 15;50(2):91-106
15630704
J Neuroimmune Pharmacol. 2008 Dec;3(4):275-85
18815890
J Neurochem. 2007 Feb;100(3):567-86
17173547
Biochem Pharmacol. 2009 Jun 1;77(11):1655-64
19161986
Neuroscience. 2007 Jun 8;146(4):1546-54
17478053
Mol Cell Neurosci. 2004 Nov;27(3):322-31
15519246
J Neurovirol. 2003 Jun;9(3):358-71
12775419
J Neurobiol. 2001 Mar;46(4):265-80
11180154
J Pediatr. 1995 May;126(5 Pt 1):710-5
7751993
Neuroreport. 2003 Jul 1;14(9):1191-5
12824758
Nat Neurosci. 2006 Feb;9(2):268-75
16415867
Nat Rev Microbiol. 2004 May;2(5):401-13
15100693
Rev Neurosci. 2002;13(3):221-42
12405226
J Neurochem. 2009 Mar;108(6):1343-59
19154336
Glia. 2003 Aug;43(2):119-27
12838504
J Neurochem. 2003 Jun;85(5):1299-311
12753088
Int J Cancer. 2009 Jan 15;124(2):326-32
19003962
Ann Neurol. 1998 Nov;44(5):831-5
9818943
Nature. 1990 Oct 18;347(6294):669-71
1699135
J Biol Chem. 1999 Jun 11;274(24):17098-102
10358063
Am J Pathol. 2000 Apr;156(4):1441-53
10751368
Gene. 2005 Sep 26;358:31-8
15958282
J Biol Chem. 1999 Apr 2;274(14):9617-26
10092648
J Cell Physiol. 2007 Sep;212(3):702-9
17477371
PLoS One. 2008 Apr 02;3(4):e1886
18382669
AIDS. 2007 Nov 12;21(17):2271-81
18090275
AIDS Read. 2002 Feb;12(2):69-74
11905143
Mol Pharmacol. 2006 Sep;70(3):1087-98
16790532
Virus Res. 2005 Aug;111(2):194-213
15885841
Nature. 2001 Apr 19;410(6831):988-94
11309629
Neuron. 2006 Feb 16;49(4):489-502
16476660
J Virol. 2004 Jul;78(14):7319-28
15220405
AIDS. 1999 Jan 14;13(1):1-22
10207540
Adv Neuroimmunol. 1994;4(3):189-93
7874386
J Nat Prod. 2004 Jun;67(6):1036-8
15217290
Glia. 2006 Dec;54(8):815-25
16977605
J Neuroimmunol. 2005 Mar;160(1-2):68-76
15710459
Curr HIV Res. 2003 Oct;1(4):463-73
15049431
J Neurosci. 2009 Feb 11;29(6):1657-69
19211873
Neuroscience. 1999;91(4):1369-78
10391443
J Neurochem. 2000 Jun;74(6):2373-9
10820198
Glia. 2008 Oct;56(13):1414-27
18551626
J NeuroAIDS. 1999;2(2):1-13
16873189
FEBS Lett. 1996 Apr 15;384(2):135-7
8612809
Brain. 2010 Mar;133(Pt 3):808-21
20123724
PLoS One. 2008;3(12):e4093
19116667
Cell Immunol. 1996 Aug 25;172(1):77-83
8806809
J Leukoc Biol. 2003 Nov;74(5):691-701
14595004
Int J Dev Neurosci. 2001 Jul;19(4):379-85
11378298
J Virol. 2000 Oct;74(19):9214-21
10982368
J Neurovirol. 2004;10 Suppl 1:25-32
14982736
J Leukoc Biol. 1999 Apr;65(4):458-65
10204574
Stem Cells Dev. 2008 Feb;17(1):199-206
18208373
J Neurosci. 2001 Dec 15;21(24):9733-43
11739582
Glia. 2006 Jan 15;53(2):132-46
16206161
Stem Cells. 2007 Oct;25(10):2638-47
17615262
J Interferon Cytokine Res. 2007 Jan;27(1):53-64
17266444
Eur J Paediatr Neurol. 2007 Jan;11(1):1-9
17137813
Mol Cell Biol. 2004 Oct;24(20):8834-46
15456859