title: Efficient uptake and dissemination of scrapie prion protein by astrocytes and fibroblasts from adult hamster brain.
abstract: Prion infections target neurons and lead to neuronal loss. However, the role of non-neuronal cells in the initiation and spread of infection throughout the brain remains unclear despite the fact these cells can also propagate prion infectivity. To evaluate how different brain cells process scrapie prion protein (PrPres) during acute infection, we exposed neuron-enriched and non-neuronal cell cultures from adult hamster brain to fluorescently-labeled purified PrPres and followed the cultures by live cell confocal imaging over time. Non-neuronal cells present in both types of cultures, specifically astrocytes and fibroblasts, internalized PrPres more efficiently than neurons. PrPres was trafficked to late endosomal/lysosomal compartments and rapidly transported throughout the cell bodies and processes of all cell types, including contacts between astrocytes and neurons. These observations suggest that astrocytes and meningeal fibroblasts play an as yet unappreciated role in prion infections via efficient uptake and dissemination of PrPres.
authors: Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, NIAID, NIH, Hamilton, Montana 59840, United States of America.
authors: Jason R
authors: JR
authors: Hollister
authors: Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, NIAID, NIH, Hamilton, Montana 59840, United States of America.
authors: Kil Sun
authors: KS
authors: Lee
authors: Microscopy Unit, Research Technologies Branch, Rocky Mountain Laboratories, NIAID, NIH, Hamilton, Montana 59840, United States of America.
authors: David W
authors: DW
authors: Dorward
authors: Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, NIAID, NIH, Hamilton, Montana 59840, United States of America.
authors: Gerald S
authors: GS
authors: Baron
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D006224:Cricetinae; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D006801:Humans; D018613:Microscopy, Confocal; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D011328:Prions / Q000378:metabolism*; D012608:Scrapie / Q000378:metabolism* / Q000473:pathology
chemical_list: D011328:Prions
references: Glia. 1999 Mar;26(1):36-46
references: 10088670
references: Neurology. 2000 Oct 24;55(8):1075-81
references: 11071481
references: J Cell Biol. 2001 Apr 30;153(3):529-41
references: 11331304
references: Brain Res. 2001 Dec 7;921(1-2):1-11
references: 11720706
references: J Neurosci. 2002 Jan 1;22(1):183-92
references: 11756501
references: J Comp Pathol. 2002 Jan;126(1):17-29
references: 11814318
references: J Virol. 2002 Dec;76(23):12259-64
references: 12414965
references: Nat Med. 2003 Apr;9(4):453-7
references: 12612547
references: J Gen Virol. 2003 Apr;84(Pt 4):1033-45
references: 12655107
references: J Gen Virol. 2003 May;84(Pt 5):1339-50
references: 12692301
references: J Neurosci Res. 2003 May 15;72(4):527-36
references: 12704814
references: Methods Cell Biol. 2003;71:111-27
references: 12884689
references: J Neurosci. 2003 Aug 27;23(21):7789-800
references: 12944508
references: Mol Biol Cell. 1992 Aug;3(8):851-63
references: 1356522
references: Arterioscler Thromb. 1992 Nov;12(11):1235-44
references: 1420082
references: Science. 2003 Oct 31;302(5646):871-4
references: 14593181
references: Brain Res Brain Res Protoc. 2003 Oct;12(2):67-76
references: 14613807
references: Neurobiol Aging. 2003 Dec;24(8):1095-104
references: 14643381
references: Am J Pathol. 2004 Jan;164(1):143-53
references: 14695328
references: J Infect Dis. 2004 Feb 1;189(3):431-9
references: 14745700
references: Virology. 2004 Mar 1;320(1):40-51
references: 15003861
references: Proc Natl Acad Sci U S A. 2004 Aug 17;101(33):12271-6
references: 15302929
references: Neuropathol Appl Neurobiol. 2004 Aug;30(4):360-8
references: 15305981
references: J Neurosci. 2005 May 25;25(21):5207-16
references: 15917460
references: Exp Gerontol. 2005 May;40(5):426-37
references: 15919595
references: Nature. 2005 Sep 8;437(7056):257-61
references: 16148934
references: J Virol Methods. 2006 Jun;134(1-2):15-29
references: 16406559
references: Proc Natl Acad Sci U S A. 1991 Jan 15;88(2):375-9
references: 1671170
references: J Virol. 1991 Dec;65(12):6597-603
references: 1682507
references: Biochem J. 2007 Feb 15;402(1):17-23
references: 17155929
references: Proc Natl Acad Sci U S A. 2007 Jun 5;104(23):9741-6
references: 17535913
references: Nat Protoc. 2007;2(6):1490-8
references: 17545985
references: J Neurosci. 2007 Jun 13;27(24):6473-7
references: 17567808
references: Glia. 2008 Jan 15;56(2):154-63
references: 18004725
references: J Neurosci. 2008 Jan 2;28(1):264-78
references: 18171944
references: J Cell Sci. 2008 Mar 15;121(Pt 6):773-83
references: 18285446
references: Cell. 2008 Nov 14;135(4):749-62
references: 19013282
references: Glia. 2009 Jul;57(9):978-88
references: 19062178
references: Nat Cell Biol. 2009 Mar;11(3):328-36
references: 19198598
references: Neuropathol Appl Neurobiol. 2009 Jun;35(3):259-71
references: 19473293
references: Proc Natl Acad Sci U S A. 2009 Dec 1;106(48):20417-22
references: 19915150
references: J Cell Sci. 2010 Jan 15;123(Pt 2):246-55
references: 20048341
references: EMBO J. 2010 Feb 17;29(4):782-94
references: 20057357
references: Science. 2010 Feb 26;327(5969):1132-5
references: 20110469
references: J Biol Chem. 2010 May 7;285(19):14083-7
references: 20304915
references: Am J Physiol Cell Physiol. 2011 Apr;300(4):C723-42
references: 21209361
references: PLoS Pathog. 2011 Mar;7(3):e1001317
references: 21437239
references: Biochemistry. 2011 May 31;50(21):4479-90
references: 21539311
references: PLoS One. 2011;6(5):e20384
references: 21647368
references: Neuron. 2011 Sep 8;71(5):799-811
references: 21903074
references: J Gen Virol. 2012 Mar;93(Pt 3):668-80
references: 22090211
references: J Neurosci. 2012 Apr 25;32(17):5821-32
references: 22539844
references: Proc Natl Acad Sci U S A. 2012 May 29;109(22):8546-51
references: 22586108
references: J Neurosci. 2012 May 23;32(21):7345-55
references: 22623680
references: FASEB J. 2012 Sep;26(9):3854-61
references: 22661006
references: Proc Natl Acad Sci U S A. 2012 Jul 10;109(28):E1938-46
references: 22711839
references: Cell Tissue Res. 2012 Oct;350(1):127-34
references: 22821398
references: J Virol. 2012 Nov;86(21):11763-78
references: 22915801
references: Science. 2013 Jan 11;339(6116):197-200
references: 23307741
references: J Biol Chem. 1990 Jul 25;265(21):12722-7
references: 2373709
references: Virology. 2014 Feb;450-451:324-35
references: 24503096
references: Acta Neuropathol Commun. 2014 Mar 31;2:32
references: 24685293
references: J Neurosci. 1986 Aug;6(8):2163-78
references: 3018187
references: J Neurosurg. 1988 Nov;69(5):766-9
references: 3054015
references: J Cell Biol. 1980 Jun;85(3):890-902
references: 6248568
references: Cell. 1983 Nov;35(1):57-62
references: 6414721
references: Neuron. 1995 Nov;15(5):1183-91
references: 7576660
references: Vet Pathol. 1995 May;32(3):299-308
references: 7604497
references: Brain Res. 1994 Sep 12;656(2):329-43
references: 7820594
references: Nature. 1976 May 13;261(5556):144-5
references: 818568
references: J Neurosci Methods. 1997 Feb;71(2):143-55
references: 9128149
references: EMBO J. 1997 Oct 15;16(20):6057-65
references: 9321385
references: J Virol. 1998 Nov;72(11):9413-8
references: 9765500
references: Nat Med. 1998 Oct;4(10):1157-65
references: 9771749
references: Brain Res. 1998 Nov 2;809(2):277-87
references: 9853120