The Enigma of Slow Viruses: Facts and Artefacts

289 Pages·1993·7.076 MB·English

by  Dr. Pawel P. Liberski (auth.)

Archives
Vfrology
Supplementum 6
P. P. Liberski
The Enigma of Slow Viruses
Facts and Artefacts
Springer-Verlag Wien New York
Dr. Pawel P. Liberski
Electron Microscopic Laboratory
Department of Oncology
Medical Academy Lodz
Lodz, Poland
This work is subject to copyright.
All rights are reserved, whether the whole or part of the material is concerned, specifically
those of translation, reprinting, re-use of illustrations, broadcasting, reproduction by
photocopying machine or similar means, and storage in data banks.
© 1993 by Springer-Verlag/Wien
Typesetting: Best-set Typesetter Ltd, Hong Kong
Printed on acid-free paper
With 56 Figures
ISSN 0939-1983
ISBN-13: 978-3-211-82427-6 e-ISBN-13: 978-3-7091-9270-2
DOl: 10.1007/978-3-7091-9270-2
This book is dedicated to
Dr. Carleton Gajdusek
on the occasion of his 70th birthday
Preface
After my return to Poland having spent several years in the Laboratory
of Central Nervous System Studies of the National Institute of Health,
Bethesda, USA I moved after a period of time to one of the very
few islands in Poland not devastated by the communist mentality, the
Department of Oncology, Medical Academy, Lodz created by Prof.
Leszek Wozniak. At the same time I suggested this review to Prof.
H.-D. Klenk, the editor of the special issue of Archives of Virology.
Such a work was not possible without the invaluable assistance of
many investigators who read chapters or generously provided scientific
materials or illustrations: Prof. Jan Albrecht, Polish Academy of
Sciences, Warsaw, Poland; Dr. David M. Asher, Laboratory of Central
Nervous System Studies, NIH, Bethesda, USA; Dr. Jan Boellaard,
University of Tiibingen, Federal Republic of Germany; Dr. Paul Brown,
Laboratory of Central Nervous System Studies, NIH, Bethesda, USA;
Prof. Herbert Budka, Neurological Institute of Vienna University,
Austria; Dr. D. Carleton Gajdusek, Laboratory of Central Nervous
System Studies, NIH, Bethesda, USA; Dr. Clarence J. Gibbs, Jr,
Laboratory of Central Nervous System Studies, NIH, Bethesda, USA;
Dr. Peter Gibson, formerly with the Neuropathogenesis Unit,
Edinburgh, Scotland; Dr. Lev Goldfarb, Laboratory of Central Nervous
System Studies, NIH, Bethesda, USA; Dr. Hugh Fraser, Neuropatho
genesis Unit, Edinburgh, Scotland; Dr. James Hope, Neuropathogenesis
Unit, Edinburgh, Scotland; Dr. Richard H. Kimberlin, SARDAS,
Edinburgh, Scotland; Prof. Laura Manuelidis, Yale University, USA;
Prof. Stanley B. Prusiner, University of California San Francisco, USA;
Dr. Gerald A.H. Wells, Central Veterinary Laboratory, Ministry of
Agriculture, Fisheries and Food, U.K., Dr. Richard Yanagihara,
Laboratory of Central Nervous System Studies, NIH, Bethesda, USA. A
few of them, however, preferred to stay anonymous. This work could
not have been accomplished without generous support from the Fogarty
International Center and the National Institutes of Health while in USA,
and the Neurological Institute, University of Vienna, Austria. Prof.
Miroslaw J. Mossakowski and the Polish Academy of Sciences, Warsaw,
is acknowledged for support while in Poland. Last but not least, I
acknowledge the continuous support and encouragement from my
Vlll Preface
collaborators in Poland: Prof. Janusz Alwasiak, Department of
Oncology, Lodz, Poland; Dr. Maria Barcikowska, Polish Academy of
Sciences, Warsaw; Prof. Hubert Kwiecinski, Department of Neurology,
Warsaw; Dr. Barbara Mirecka, Department of Oncology, Lodz; Prof.
Wielislaw Papierz, Department of Pathological Anatomy, Lodz; and the
skilful technical assistance of Ryszard Kurczewski, Elzbieta Naganska,
Leokadia Romanska and Kazimierz Smoktunowicz.
Pawel P. Liberski
Contents
Abbreviations .............................................. Xlll
1. Introduction: subacute spongiform virus
encephalopathies from the perspective
of a neuroscientist ................................. . 1
2. The molecular biology of the slow viruses ............. . 7
2.1. The search for the virus-specific nucleic acid .......... . 7
2.1.1. Radiation experiments ............................ . 8
2.1.2. Fruitless attempts to isolate scrapie-specific infectious
nucleic acid ...................................... . 11
2.2. The prion protein ................................. . 18
2.2.1. The purification of the PrP 27-30, PrP 33-35sC and PrP
33-35c .......................................... . 18
2.2.1.1. Strategies used to purify the scrapie virus and scrapie
specific protein ................................... . 18
2.2.1.2. Purification of the PrP27-30 ....................... . 19
2.2.1.3. PrP proteins are disease-specific for the whole group
of unconventional slow virus disorders ............... . 21
2.2.1.4. PrP 33-35sC and PrP 33-35c •••.••.•..••••.•••••.••• 23
2.2.2. The structure of the PrP proteins ................... . 25
2.2.2.1. N-terminal sequence of the PrP ..................... . 25
2.2.2.2. The secondary structure of the PrP .................. . 28
2.2.3. Postranslational modifications of the PrP ............. . 31
2.2.4. Functional studies of the PrP proteins ............... . 34
2.2.5. The scrapie associated fibrils or prion rods ........... . 35
2.2.5.1. The chemical composition of SAF .................. . 41
2.3. The structure of the gene encoding PrP 33-35 (Prn-p)
in different species ................................ . 46
2.3.1. The hamster Prn-p gene ........................... . 46
2.3.2. The murine Prn-p gene ............................ . 48
2.3.3. The rat Prn-p gene ................................ . 49
2.3.4. The human Prn-p gene (PRNP) .................... . 50
x Contents
2.3.5. The ovine and bovine Prn-p gene . . . . . . . . . . . . . . . . . . . . 50
2.3.6. The avian analogue of the Prn-p gene ................ 54
2.3.7. The linkage of genes controlling the incubation period
and susceptibility to scrapie and Creutzfeldt-Jakob
disease (CJD) to the gene encoding
PrP 33-35 (Prn-p) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54
2.3.7.1. Prn-i and Sine in mice. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55
2.3.7.2. Prn-i and Sip gene in sheep ......................... 60
2.3.8. The linkage of Gerstmann-Straussler-Scheinker
syndrome (GSSS) to the PrP (PRNP) gene. . . . . . . . . . . . 62
2.3.9. Familial CJD. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66
2.3.10. The association of CJD cases of Eastern European
origin and in Sephardic Jews with a mutation of the PrP
gene at codon 200 ................................. 68
2.3.11. Other PrP gene mutations associated with sporadic
and familial CJD cases ............................. 71
2.3.12. A 0.15 kb insertion within the PrP gene observed
with CJD and GSSS cases. . . . . . . . . . . . . . . . . . . . . . . . . . . 72
2.3.13. The codon 178 mutation in familial CJD . . . . . . . . . . . . . . 73
2.4. The models of slow viruses. . . . . . . . . . . . . . . . . . . . . . . . . . 73
2.4.1. Strains of scrapie virus ............................. 74
2.4.2. The prion-only hypothesis .......................... 78
2.4.3. Virino and conventional virus hypothesis ............. 80
3. The pathogenesis of slow virus infection . . . . . . . . . . . . . . . 83
3.1. The general sequence of the pathogenetic events. . . . . . . 83
3.2. The role of the spleen . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85
3.3. The role of the spleen in neuroinvasion . . . . . . . . . . . . . . . 87
3.4. The role of viremia ................................ 93
3.5. The role of macrophages in scrapie infection .......... 95
3.6. The neural spread of infectivity from the spleen to the
central nervous system ............................. 95
3.7. The neural spread of infectivity within the central
nervous system . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 98
3.8. Biochemistry and histochemistry of slow virus
infections. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 100
3.8.1. Neurotransmitters alterations ....................... 100
3.8.1.1. Cholinergic system. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 100
3.8.1.2. Monoaminergic systems. . . . . . . . . . . . . . . . . . . . . . . . . . .. 101
3.8.1.3. Histaminergic system. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 103
3.8.1.4. GABAergic system . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 103
3.8.2. Oxydative and lysosomal enzymes ................... 104
3.8.2. Immunology of slow virus infections. . . . . . . . . . . . . . . . .. 106
Contents Xl
3.8.2.1. Autoantibodies against neurofiament proteins ........ . 106
3.8.2.2. Increased concentration of IgG in serum of scrapie-
affected sheep .................................... . 108
4. Neuropathology of slow virus diseases ................ . 111
4.1. Natural scrapie ................................... . 111
4.2. Kuru ............................................ . 112
4.3 Creutzfeldt-lakob disease (C1D) .................... . 114
4.3.1. Introduction ..................................... . 114
4.3.2. Classifications .................................... . 114
4.3.3. Classical C1D .................................... . 115
4.3.4. Ataxic form of C1D ............................... . 117
4.3.5. Gerstmann-Stdiussler-Scheinker (GSS) syndrome ..... . 118
4.3.6. Panencephalopathic form of C1D ................... . 119
4.3.7. Amyotrophic form of C1D ......................... . 120
4.3.8. C1D and other neurological disorders ............... . 120
4.4. Elements of neuropathology of slow virus disorders ... . 121
4.4.1. Spongiform vacuoles .............................. . 121
4.4.1.1. Introduction ..................................... . 121
4.4.1.2. Distribution of vacuoles within grey and white
matter: lesion profile .............................. . 121
4.4.1.3. Ultrastructure of vacuoles ......................... . 123
4.4.1.3.1. Creutzfeldt-lakob disease (C1D) .................... . 123
4.4.1.3.2. Scrapie, bovine spongiform encephalopathy (BSE)
and chronic wasting disease ........................ . 129
4.4.1.3.3. Ultrastructure of intramyelin vacuoles in the
panencephalopathic type of C1D and other types
of subacute spongiform virus encephalopathies ....... . 130
4.4.1.4. Morphogenesis of spongiform changes ............... . 132
4.4.2. Astrocytic reaction ................................ . 134
4.4.2.l. Introduction ..................................... . 134
4.4.2.2. Kuru, Creutzfeldt-lakob disease and Gerstmann-
Stdiussler-Scheinker syndrome ..................... . 135
4.4.2.2.1. Kuru ............................................ . 135
4.4.2.2.2. Creutzfeldt-lakob disease (C1D) and Gerstmann-
Straussler-Scheinker syndrome (GSSS) .............. . 136
4.4.2.2.3. The involvement of astrocytes in formation of amyloid
plaques .......................................... . 139
4.4.2.4. Scrapie, bovine spongiform encephalopathy (BSE),
and chronic wasting disease ........................ . 139
4.4.2.5. The blood-brain-barrier in slow virus diseases ........ . 144
4.4.2.6 The particular forms of astrocytic reaction
in unconventional slow virus diseases ................ . 145