Fatal Transmissible Amyloid Encephalopathy: A New Type of Prion Disease Associated with Lack of Prion Protein Membrane Anchoring
Prion diseases are fatal neurodegenerative diseases of humans and animals characterized by gray matter spongiosis and accumulation of aggregated, misfolded, protease-resistant prion protein (PrPres). PrPres can be deposited in brain in an amyloid-form and/or non-amyloid form, and is derived from host-encoded protease-sensitive PrP (PrPsen), a protein normally anchored to the plasma membrane by glycosylphosphatidylinositol (GPI). Previously, using heterozygous transgenic mice expressing only anchorless PrP, we found that PrP anchoring to the cell membrane was required for typical clinical scrapie. However, in the present experiments, using homozygous transgenic mice expressing two-fold more anchorless PrP, scrapie infection induced a new fatal disease with unique clinical signs and altered neuropathology, compared to non-transgenic mice expressing only anchored PrP. Brain tissue of transgenic mice had high amounts of infectivity, and histopathology showed dense amyloid PrPres plaque deposits without gray matter spongiosis. In contrast, infected non-transgenic mice had diffuse non-amyloid PrPres deposits with significant gray matter spongiosis. Brain graft studies suggested that anchored PrPsen expression was required for gray matter spongiosis during prion infection. Furthermore, electron and light microscopic studies in infected transgenic mice demonstrated several pathogenic processes not seen in typical prion disease, including cerebral amyloid angiopathy and ultrastructural alterations in perivascular neuropil. These findings were similar to certain human familial prion diseases as well as to non-prion human neurodegenerative diseases, such as Alzheimer's disease.
Vyšlo v časopise:
Fatal Transmissible Amyloid Encephalopathy: A New Type of Prion Disease Associated with Lack of Prion Protein Membrane Anchoring. PLoS Pathog 6(3): e32767. doi:10.1371/journal.ppat.1000800
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.ppat.1000800
Souhrn
Prion diseases are fatal neurodegenerative diseases of humans and animals characterized by gray matter spongiosis and accumulation of aggregated, misfolded, protease-resistant prion protein (PrPres). PrPres can be deposited in brain in an amyloid-form and/or non-amyloid form, and is derived from host-encoded protease-sensitive PrP (PrPsen), a protein normally anchored to the plasma membrane by glycosylphosphatidylinositol (GPI). Previously, using heterozygous transgenic mice expressing only anchorless PrP, we found that PrP anchoring to the cell membrane was required for typical clinical scrapie. However, in the present experiments, using homozygous transgenic mice expressing two-fold more anchorless PrP, scrapie infection induced a new fatal disease with unique clinical signs and altered neuropathology, compared to non-transgenic mice expressing only anchored PrP. Brain tissue of transgenic mice had high amounts of infectivity, and histopathology showed dense amyloid PrPres plaque deposits without gray matter spongiosis. In contrast, infected non-transgenic mice had diffuse non-amyloid PrPres deposits with significant gray matter spongiosis. Brain graft studies suggested that anchored PrPsen expression was required for gray matter spongiosis during prion infection. Furthermore, electron and light microscopic studies in infected transgenic mice demonstrated several pathogenic processes not seen in typical prion disease, including cerebral amyloid angiopathy and ultrastructural alterations in perivascular neuropil. These findings were similar to certain human familial prion diseases as well as to non-prion human neurodegenerative diseases, such as Alzheimer's disease.
Zdroje
1. AguzziA
PolymenidouM
2004 Mammalian prion biology: one century of evolving concepts. Cell 116 313 327
2. Di BariMA
ChianiniF
VaccariG
EspositoE
ConteM
2008 The bank vole (Myodes glareolus) as a sensitive bioassay for sheep scrapie. J Gen Virol 89 2975 2985
3. NonnoR
Di BariMA
CardoneF
VaccariG
FazziP
2006 Efficient transmission and characterization of Creutzfeldt-Jakob disease strains in bank voles. PLoS Pathog 2 e12 doi:10.1371/journal.ppat.0020012
4. JeffreyM
GoodsirCM
BruceME
McBridePA
FraserJR
1997 In vivo toxicity of prion protein in murine scrapie: ultrastructural and immunogold studies. Neuropathol Appl Neurobiol 23 93 101
5. GonzalezL
MartinS
Begara-McGorumI
HunterN
HoustonF
2002 Effects of agent strain and host genotype on PrP accumulation in the brain of sheep naturally and experimentally affected with scrapie. J Comp Pathol 126 17 29
6. GhettiB
PiccardoP
FrangioneB
BugianiO
GiacconeG
1996 Prion protein amyloidosis. Brain Pathol 6 127 145
7. ErsdalC
GoodsirCM
SimmonsMM
McGovernG
JeffreyM
2009 Abnormal prion protein is associated with changes of plasma membranes and endocytosis in bovine spongiform encephalopathy (BSE)-affected cattle brains. Neuropathol Appl Neurobiol 35 259 271
8. ParchiP
ChenSG
BrownP
ZouW
CapellariS
1998 Different patterns of truncated prion protein fragments correlate with distinct phenotypes in P102L Gerstmann-Straussler-Scheinker disease. Proc Natl Acad Sci U S A 95 8322 8327
9. PiccardoP
DlouhySR
LievensPM
YoungK
BirdTD
1998 Phenotypic variability of Gerstmann-Straussler-Scheinker disease is associated with prion protein heterogeneity. J Neuropathol Exp Neurol 57 979 988
10. PiccardoP
SeilerC
DlouhySR
YoungK
FarlowMR
1996 Proteinase-K-resistant prion protein isoforms in Gerstmann-Straussler-Scheinker disease (Indiana kindred). J Neuropathol Exp Neurol 55 1157 1163
11. GiacconeG
VergaL
BugianiO
FrangioneB
SerbanD
1992 Prion protein preamyloid and amyloid deposits in Gerstmann- Straussler- Scheinker disease, Indiana kindred [published erratum appears in Proc Natl Acad Sci U S A 1993 Jan 1;90(1):302]. Proc Natl Acad Sci U S A 89 9349 9353
12. BruceME
DickinsonAG
1985 Genetic control of amyloid plaque production and incubation period in scrapie-infected mice. J Neuropathol Exp Neurol 44 285 294
13. JeffreyM
GoodsirCM
BruceME
McBridePA
ScottJR
1992 Infection specific prion protein (PrP) accumulates on neuronal plasmalemma in scrapie infected mice. Neurosci Lett 147 106 109
14. ReveszT
GhisoJ
LashleyT
PlantG
RostagnoA
2003 Cerebral amyloid angiopathies: a pathologic, biochemical, and genetic view. J Neuropathol Exp Neurol 62 885 898
15. WellerRO
SubashM
PrestonSD
MazantiI
CarareRO
2008 Perivascular drainage of amyloid-beta peptides from the brain and its failure in cerebral amyloid angiopathy and Alzheimer's disease. Brain Pathol 18 253 266
16. StahlN
BorcheltDR
PrusinerSB
1990 Differential release of cellular and scrapie prion proteins from cellular membranes by phosphatidylinositol-specific phospholipase C. Biochemistry 29 5405 5412
17. JeffreyM
GoodsirCM
BruceM
McBridePA
ScottJR
1994 Correlative light and electron microscopy studies of PrP localisation in 87V scrapie. Brain Res 656 329 343
18. JeffreyM
McGovernG
GoodsirCM
SisoS
GonzalezL
2009 Strain-associated variations in abnormal PrP trafficking of sheep scrapie. Brain Pathol 19 1 11
19. ChesebroB
TrifiloM
RaceR
Meade-WhiteK
TengC
2005 Anchorless prion protein results in infectious amyloid disease without clinical scrapie. Science 308 1435 1439
20. PrusinerSB
ScottM
FosterD
PanKM
GrothD
1990 Transgenetic studies implicate interactions between homologous PrP isoforms in scrapie prion replication. Cell 63 673 686
21. MansonJC
ClarkeAR
McBridePA
McConnellI
HopeJ
1994 PrP gene dosage determines the timing but not the final intensity or distribution of lesions in scrapie pathology. Neurodegen 3 331 340
22. TagliaviniF
PrelliF
GhisoJ
BugianiO
SerbanD
1991 Amyloid protein of Gerstmann-Straussler-Scheinker disease (Indiana kindred) is an 11 kd fragment of prion protein with an N-terminal glycine at codon 58. EMBO J 10 513 519
23. JeffreyM
ScottJR
FraserH
1991 Scrapie inoculation of mice: light and electron microscopy of the superior colliculi. Acta Neuropathol 81 562 571
24. JeffreyM
GoodsirCM
RaceRE
ChesebroB
2004 Scrapie-specific neuronal lesions are independent of neuronal PrP expression. Ann Neurol 55 781 792
25. OkabeM
IkawaM
KominamiK
NakanishiT
NishimuneY
1997 ‘Green mice’ as a source of ubiquitous green cells. FEBS Lett 407 313 319
26. BrandnerS
IsenmannS
RaeberA
FischerM
SailerA
1996 Normal host prion protein necessary for scrapie-induced neurotoxicity. Nature 379 339 343
27. CampanaV
CaputoA
SarnataroD
PaladinoS
TivodarS
2007 Characterization of the properties and trafficking of an anchorless form of the prion protein. J Biol Chem 282 22747 22756
28. StahlN
BaldwinMA
BurlingameAL
PrusinerSB
1990 Identification of glycoinositol phospholipid linked and truncated forms of the scrapie prion protein. Biochemistry 29 8879 8884
29. PiccardoP
MansonJC
KingD
GhettiB
BarronRM
2007 Accumulation of prion protein in the brain that is not associated with transmissible disease. Proc Natl Acad Sci U S A 104 4712 4717
30. TuziNL
CancellottiE
BaybuttH
BlackfordL
BradfordB
2008 Host PrP glycosylation: a major factor determining the outcome of prion infection. PLoS Biol 6 e100 doi:10.1371/journal.pbio.0060100
31. RaceB
Meade-WhiteK
OldstoneMB
RaceR
ChesebroB
2008 Detection of prion infectivity in fat tissues of scrapie-infected mice. PLoS Pathog 4 e1000232 doi:10.1371/journal.ppat.1000232
32. GhettiB
PiccardoP
SpillantiniMG
IchimiyaY
PorroM
1996 Vascular variant of prion protein cerebral amyloidosis with tau-positive neurofibrillary tangles: the phenotype of the stop codon 145 mutation in PRNP. Proc Natl Acad Sci U S A 93 744 748
33. ReveszT
HoltonJL
LashleyT
PlantG
FrangioneB
2009 Genetics and molecular pathogenesis of sporadic and hereditary cerebral amyloid angiopathies. Acta Neuropathol 118 115 130
34. JansenC
ParchiP
CapellariS
VermeijAJ
CorradoP
2009 Prion protein amyloidosis with divergent phenotype associated with two novel nonsense mutations in PRNP. Acta Neuropathol
35. DyckRF
LockwoodCM
KershawM
McHughN
DuanceVC
1980 Amyloid P-component is a constituent of normal human glomerular basement membrane. J Exp Med 152 1162 1174
36. PflanzH
VanaK
MittereggerG
PaceC
MessowD
2009 Microinjection of lentiviral vectors expressing small interfering RNAs directed against laminin receptor precursor mRNA prolongs the pre-clinical phase in scrapie-infected mice. J Gen Virol 90 269 274
37. PflanzH
VanaK
MittereggerG
Renner-MullerI
PaceC
2009 Scrapie-infected transgenic mice expressing a laminin receptor decoy mutant reveal a prolonged incubation time associated with low levels of PrPres. J Mol Biol 388 721 729
38. CaugheyB
BrownK
RaymondGJ
KatzenstienGE
ThresherW
1994 Binding of the protease-sensitive form of PrP (prion protein) to sulfated glycosaminoglycan and Congo red. J Virol 68 2135 2141
39. KimberlinRH
WalkerCA
1986 Suppression of scrapie infection in mice by heteropolyanion 23, dextran sulfate, and some other polyanions. Antimicrob Agents Chemother 30 409 413
40. LadoganaA
CasacciaP
IngrossoL
CibatiM
SalvatoreM
1992 Sulphate polyanions prolong the incubation period of scrapie-infected hamsters. J Gen Virol 73 661 665
41. DiringerH
EhlersB
1991 Chemoprophylaxis of scrapie in mice. J Gen Virol 72 457 460
42. Doh-uraK
IshikawaK
Murakami-KuboI
SasakiK
MohriS
2004 Treatment of Transmissible Spongiform Encephalopathy by Intraventricular Drug Infusion in Animal Models. J Virol 78 4999 5006
43. FarquharCF
DickinsonAG
1986 Prolongation of scrapie incubation period by an injection of dextran sulphate 500 within the month before or after infection. J Gen Virol 67 463 473
44. Larramendy-GozaloC
BarretA
DaudigeosE
MathieuE
AntonangeliL
2007 Comparison of CR36, a new heparan mimetic, and pentosan polysulfate in the treatment of prion diseases. J Gen Virol 88 1062 1067
45. WongC
XiongL-W
HoriuchiM
RaymondLD
WehrlyK
2001 Sulfated glycans and elevated temperature stimulate PrPSc dependent cell-free formation of protease-resistant prion protein. EMBO J 20 377 386
46. BaronGS
WehrlyK
DorwardDW
ChesebroB
CaugheyB
2002 Conversion of raft associated prion protein to the protease-resistant state requires insertion of PrP-res (PrP(Sc)) into contiguous membranes. EMBO J 21 1031 1040
47. BaronGS
CaugheyB
2003 Effect of glycosylphosphatidylinositol anchor-dependent and - independent prion protein association with model raft membranes on conversion to the protease-resistant Isoform. J Biol Chem 278 14883 14892
48. CaugheyB
RaymondGJ
1993 Sulfated polyanion inhibition of scrapie-associated PrP accumulation in cultured cells. J Virol 67 643 650
49. MansonJC
ClarkeAR
HooperML
AitchisonL
McConnellI
1994 129/Ola mice carrying a null mutation in PrP that abolishes mRNA production are developmentally normal. Mol Neurobiol 8 121 127
50. RaceBL
Meade-WhiteKD
WardA
JewellJ
MillerMW
2007 Levels of abnormal prion protein in deer and elk with chronic wasting disease. Emerg Infect Dis 13 824 830
51. Meade-WhiteK
RaceB
TrifiloM
BossersA
FavaraC
2007 Resistance to chronic wasting disease in transgenic mice expressing a naturally occurring allelic variant of deer prion protein. J Virol 81 4533 4539
52. KercherL
FavaraC
StriebelJF
LaCasseR
ChesebroB
2007 Prion protein expression differences in microglia and astroglia influence scrapie-induced neurodegeneration in the retina and brain of transgenic mice. J Virol 81 10340 10351
53. JeffreyM
GoodsirCM
FowlerN
HopeJ
BruceME
1996 Ultrastructural Immuno-localization of Synthetic Prion Protein Peptide Antibodies in 87V Murine Scrapie. Neurodegen 5 101 109
54. CaugheyB
RaymondGJ
ErnstD
RaceRE
1991 N-terminal truncation of the scrapie-associated form of PrP by lysosomal protease(s): implications regarding the site of conversion of PrP to the protease-resistant state. J Virol 65 6597 6603
Štítky
Hygiena a epidemiológia Infekčné lekárstvo LaboratóriumČlánok vyšiel v časopise
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