Neurovirology: Viruses and the Brain (eBook)

Cover 1
Contents 6
Part 1: Basic Models 16
Chapter 1. Genetic Determinants of Neurovirulence of Murine Oncornaviruses 18
I. Introduction 18
II. Clinicopathological Manifestations of Neurovirulent Murine Oncornavirus Infection 21
III. Mapping of Viral Determinants of Neurologic Disease 23
IV. Viral Sequences that Determine Neuroinvasiveness 27
V. Host Factors and Neuroinvasiveness 30
VI. Viral Envelope Sequences that Determine Neurotoxicity 32
VII. Cell Types Involved in Neurovirulence 36
VIII. Envelope Expression in Microglia 38
IX. Role of Inflammation 40
X. Retroviruses and Multiple Sclerosis 42
XI. Concluding Remarks 44
References 44
Chapter 2. Pseudorabies Virus Neuroinvasiveness: A Window into the Functional Organization of the Brain 54
I. Viruses and the Nervous System 54
II. Neuronal Architecture and Neurotropic Viruses 56
III. Importance of Using Well-Characterized Strains of Virus 59
IV. Replication and Intracellular Spread of Pseudorabies Virus in the Brain 61
V. Brain Defenses and Neuroinvasiveness 72
VI. Recombinant Viruses and the Nervous System 77
VII. Viral Circuit Analysis: Future Applications 80
VIII. Conclusions 81
References 81
Chapter 3. Neurovirology and Developmental Neurobiology 88
I. Introduction 88
II. Central Nervous System Development 89
III. Virus Replication 94
IV. Alphavirus Infections as Examples of Age-Related Neurovirulence 97
V. Virus Infections of Developing Nervous System 112
VI. Other Important Infections of the Developing Human Central Nervous System 120
References 124
Part 2: Viral Immune Responses in the Central Nervous System 140
Chapter 4. Chemokines and Viral Diseases of the Central Nervous System 142
I. Introduction 142
II. Chemokines and their Receptors: An Overview 144
III. Chemokines and their Receptors in the Central Nervous System 154
IV. Chemokines and their Receptors in Viral Diseases of the Central Nervous System 158
V. Concluding Remarks 172
References 174
Chapter 5. Regulation of T Cell Responses During Central Nervous System Viral Infection 190
I. Introduction 190
II. Effector Functions of T Cells during CNS Viral Infection 191
III. Regulation of T Cell Responses during CNS Viral Infection 194
IV. Concluding Remarks 207
References 209
Chapter 6. Virus-Induced Autoimmunity: Epitope Spreading to Myelin Autoepitopes in Theiler’s Virus Infection of the Central Nervous System 214
I. Introduction 214
II. Relevance of Murine TMEV-Induced Demyelinating Disease to Human Multiple Sclerosis 216
III. TMEV Infection as Model of Persistent Virus-Induced, CD4+ T Cell-Mediated Demyelination 216
IV. Virus-Specific CD4+ T Cell Respones Initiate Disease 219
V. Myelin-Specific CD4+ T Cell Responses: Pathologic Role in Chronic Theiler’s Virus-Induced Demyelinating Disease 219
VI. Myelin Epitope-Specific CD4+ T Cell Responses in TMEV-Infected Mice Arising via Epitope Spreading 223
VII. Endogenous Presentation of Virus and Myelin Epitopes by CNS-Resident Antigen-Presenting C in TMEV-Infected Mice 224
VIII. Summary 226
References 227
Chapter 7. Selection of and Evasion from Cytotoxic T Cell Responses in the Central Nervous System 234
I. Objectives of this Review 234
II. Introduction 235
III. Selection of CTL Escape Mutants in Viral Encephalomyelitis 241
IV. Conclusions and Future Directions 249
References 251
Chapter 8. DNA Immunization and Central Nervous System Viral Infection 258
I. Virus Infections of the Central Nervous System 259
II. Antiviral Immune Response 264
III. Central Nervous System as a Haven for Viruses 271
IV. Vaccinating Against Virus-Induced CNS Diseases: An Introduction to Mouse Models 273
V. DNA Vaccines and CNS Viral Infections 277
References 281
Part 3: Spongiform Encephalopathies 290
Chapter 9. Transmissible Spongiform Encephalopathies and Prion Proten Interconversions 292
I. Introduction 292
II. Tranmissible Spongiform Encephalopathies in Humans and Animals 294
III. Prion Protein: Cellular and Molecular Aspects 300
IV. Current Issues in TSE Research 310
References 317
Chapter 10. Spongiform Encephalopathies: Insights from Transgenic Models 328
I. Introduction 328
II. Transgenic Models for Human Hereditary Prion Diseases 332
III. Mice as Transgenic Models 334
IV. Structure-Function Studies on PrP Gene 337
V. Species Barrier. 340
VI. Prion Strains 343
VII. Ectopic Expression of PrP in PrnP-Ablated Mice 345
VIII. Prions and the Central Nervous System 347
IX. Conclusion 357
References 358
Part 4: HIV: Human Immunodeficiency Virus 368
Chapter 11. The Blood–Brain Barrier and AIDS 370
I. Introduction 370
II. AIDS Dementia versus HIV Encephalitis 372
III. Timing of Viral Entry into the CNS 375
IV. Mechanisms and Models of Viral Entry 375
V. The Central Nervous System as a Viral Reservoir 383
VI. Animal Models 386
References 395
Chapter 12. Neuroimmune and Neurovirological Aspects of Human Immunodeficiency Virus Infection 404
I. Introduction 404
II. Clinical Aspects 407
III. Virological Aspects 414
IV. Neuropathogenesis 415
V. Animal Models 430
VI. Unanswered Questions 432
VII. Summary 433
References 433
Chapter 13. Simian Immunodeficiency Virus Model of HIV-Induced Central Nervous System Dysfunction 450
I. Introduction 450
II. Animal Models 452
III. Brain Infection 460
IV. Host Responses 461
V. Chemokines and Their Receptors 467
VI. Central Nervous System Dysfunction 469
VII. Chemotherapy and Prophylaxis 472
VIII. Conclusion 473
References 474
Chapter 14. Neuroendocrine-Immune Interactions during Viral Infections 484
I. Introduction 484
II. Hypothalamic–Pituitary–Adrenal (HPA) Axis 485
III. Glucocorticoid Induction during Viral Infections: Mechanisms and Signaling Pathways 489
IV. Impact of Glucocorticoids on Target Tissues 506
V. Role of HPA in Shaping Immune Response during Viral Infection 509
VI. Conclusions 515
References 515
Part 5: Preclinical and Clincal Models 530
Chapter 15. Role of Viruses in Etiology and Pathogenesis of Multiple Sclerosis 532
I. Introduction 532
II. Etiology of Multiple Sclerosis 533
III. Viruses in Multiple Sclerosis 544
IV. Conclusions 558
References 559
Chapter 16. Bornavirus Tropism and Targeted Pathogenesis: Virus–Host Interactions in a Neurodevelopmental Model 572
I. Introduction 572
II. Mechanisms for Neurotropism: Phosphorylation of Borna DiseaseVirus Phosphoprotein by Protien Kinase Ce 573
III. Mechansisms for BDV Persistence 574
IV. Borna Disease Rat Models for Human Central Nervous System Disorders 576
V. Summary 591
References 591
Chapter 17. Paradigms for Behavioral Assessment of Viral Pathogenesis 598
I. Introduction 598
II. Behavioral Effects of Viral Infection in Rodents 600
III. Behavioral Effects of Viral Infection in Nonhuman Primates 614
IV. Conclusion 632
References 633
Index 642