Prokaryotic and Eukaryotic Heat Shock Proteins in Infectious Disease (eBook)

Preface 6
Contents 8
Contributors 10
1 Role of HSF1 in Infectious Disease 13
1.1 Introduction 14
1.2 The Basic Biology of HSF 14
1.2.1 Overview of HSF Structure and Function 15
1.2.2 Activation of HSF Trimerization and HSE Binding Capacity 16
1.2.3 HSF Transactivating Activity 19
1.2.4 Regulation of HSF by Covalent Modification and Heterologous Protein Binding 20
1.2.4.1 HSF Phosphorylation 20
1.2.4.2 Other Covalent Modifications of HSF 22
1.2.4.3 Heterologous Protein Interactions 22
1.3 Activation of HSF1 by Factors Associated with Infections 24
1.3.1 Activation of HSF-1 at Febrile-Range Temperatures 24
1.3.2 Activation of Heat Shock Signaling by Products of Infection 25
1.4 Alterations in Heat Shock Response During Infections 27
1.5 Consequences of HSF1 Activation During Infection 29
1.5.1 Other Biological Effects of HSF1 Activation 29
1.5.2 Heat Shock, Cellular Injury and Survival 30
1.6 Conclusion 32
2 Propagating Prions: An Essential Role for Molecular Chaperones 44
2.1 Introduction What Is a Prion? 45
2.2 Yeast Prions Proving the Prion Hypothesis 45
2.3 Role of Molecular Chaperones in Yeast Prion Propagation 46
2.3.1 Hsp104 50
2.3.2 Hsp70s 52
2.4 Role of Hsp70 Co-chaperones in Yeast Prion Propagation Direct and Indirect Effects 54
2.5 Relevance of Yeast Prions to Mammalian Prion Diseases 55
2.6 Conclusions 56
3 Role of Heat Shock Proteins in Viral Infection 62
3.1 Introduction 62
3.2 Modulation of the Heat Shock Response During Viral Infection 63
3.3 How Do Viruses Activate the Heat Shock Response? 68
3.4 Which Is the Functional Significance of HSP Induction During Viral Infection? 71
3.4.1 Virus Entry 71
3.4.2 Uncoating 72
3.4.3 Viral Gene Expression 74
3.4.4 Genome Replication 76
3.4.5 Assembly of Viral Components and Virion Morphogenesis 78
3.5 Effect of Hyperthermia and HSR Modulators on Virus Replication 79
3.5.1 Hsp90 Inhibitors and Virus Replication 79
3.5.2 Hyperthermia in Viral Infection 80
3.5.3 Induction of Heat Shock Proteins by Antiviral Agents 83
3.6 Concluding Remarks 84
4 Chaperones in the Morphogenesis of Viruses 96
4.1 Introduction 96
4.2 Hsp60: Assisting Folding in Seclusion 98
4.2.1 The Hsp60 Chaperone Chamber 98
4.2.2 GroEL Interactions with Coats and Tails 98
4.2.3 TriC: A Bag of Tricks for Virus Assembly? 101
4.3 Hsp70: Assisting Folding by Local Interactions 102
4.3.1 The Hsp70 Chaperone Team 102
4.3.2 Hsp70 in Virion Assembly 104
4.3.3 Hsp70 in Disassembly 106
4.3.4 Hsp70 as Part of the Coat 107
4.4 Hsp90: Assisting Folding by Holding 107
4.4.1 The Hsp90 Chaperone Platform 107
4.4.2 Hsp90s in Viral Development 108
4.5 Concluding Remarks 110
5 Role of Host Molecular Chaperones in Responses to Bacterial Infection and Endotoxin Exposure 117
5.1 Introduction 117
5.2 Heat Shock Proteins and Infection 119
5.3 Fever, Sepsis and the Anti-Inflammatory Influence of the HSR 122
5.4 Role of HSF1 and Heat Shock Proteins in Regulating NFB 123
5.5 Overriding the Heat Shock Response by Pro-inflammatory Signaling 124
5.6 Conclusions 125
6 Mycobacterial Heat Shock Protein 60s in the Induction and Regulation of Infectious Disease 131
6.1 Introduction 131
6.2 Mycobacterial Hsp60s 133
6.2.1 Mycobacterial Diseases 133
6.2.2 Pathology of Tuberculosis 134
6.3 Immune Responses Against Mycobacteria and Mycobacterial Cpn60s 135
6.3.1 Mycobacteria, as well as Mycobacterial Cpn60s 135
6.3.2 Antibody Responses to Cpn60s 136
6.3.3 Cellular Responses to Cpn60s and Cytokine Release 136
6.4 The Role of Hsp60 in the Pathology of Tuberculosis 137
6.5 Protective and Misdirected Immune Responses Against Mycobacterial Cpn60 Proteins 138
6.5.1 Cpn60-Based Vaccines Against Mycobacterial Diseases 138
6.5.2 Regulation of Autoimmunity by Cpn60 Proteins 139
6.5.3 Hypothesis: Granuloma Activation-Suppression Cycle 139
7 Heat Shock Proteins in Protozoan Parasites Leishmania spp. 144
7.1 The Organism 144
7.1.1 Gene Regulation in Leishmania spp. : A Farewell to Promoters 144
7.1.2 Leishmania Life Cycle and Pathogeny 145
7.1.3 Axenic Differentiation In Vitro 147
7.2 Heat Shock Proteins in Leishmania 147
7.2.1 The Heat Shock Protein Complement of Leishmania 147
7.2.2 Heat Shock Proteins and the Heat Shock Response 149
7.2.3 Stage-Specific Expression of Heat Shock Proteins in Leishmania 150
7.2.3.1 Pre-genome Era 150
7.2.3.2 Post-genome Era 150
7.3 Specific Roles in the Parasitic Life Cycle 153
7.3.1 Hsp100 153
7.3.2 Hsp90 153
7.3.3 Antogonistic roles for Hsp90 and Hsp100 154
7.3.4 Heat Shock Proteins as Antigens in Leishmania Infections 154
7.3.5 Protection Against Anti-microbial Agents 156
7.4 Future Directions 156
8 Toll-Like Receptors and Infectious Diseases: Role of Heat Shock Proteins 161
8.1 Introduction 161
8.2 Toll-Like Receptors Linked to Infectious Diseases 162
8.2.1 TLR1 163
8.2.2 TLR2 163
8.2.3 TLR3 164
8.2.4 TLR4 164
8.2.5 TLR5 166
8.2.6 TLR6 166
8.2.7 TLR7 and TLR8 167
8.2.8 TLR9 167
8.2.9 TLR11 167
8.3 Conclusion 167
9 Lipid Rafts, Lipopolysaccharide and Stress Proteins in Infectious Diseases 176
9.1 Introduction 176
9.2 Heat Shock Proteins as Intracellular Molecular Chaperones 177
9.3 Heat Shock Proteins as Extracellular Molecular Chaperones 177
9.4 Cell Surface Expression of Heat Shock Proteins 178
9.5 Lipid Rafts 178
9.6 Association of Heat Shock Proteins with Lipid Rafts 179
9.7 Role of Heat Shock Proteins in Acquired Immune Responses 180
9.8 Re-Presentation and Cross-Priming 180
9.9 Role of Heat Shock Protein in Innate Immune Responses 180
9.10 Lipopolysaccharide Recognition 181
9.11 Toll-Like Receptor Ligands? 182
9.12 Modulators of the Innate Immune Response? 183
9.13 Novel Therapeutic Interventions? 184
9.14 Concluding Remarks 184
10 Heat Shock Proteins Are Mediators of Bacterial-HostInteractions 191
10.1 The Diversity of Life on Our Earth 191
10.1.1 Bacterial Diversity 192
10.1.1.1 Bacterial Diversity in Homo Sapiens 192
10.2 BacteriaHost Interactions 193
10.3 Heat Shock Proteins 194
10.3.1 Heat Shock Proteins as Moonlighting Proteins 194
10.4 Heat Shock Proteins and the Stress of Infection 194
10.5 Host Heat Shock Proteins Can Function as Receptors for Bacteria 195
10.6 Host Heat Shock Proteins Are Found in the Circulation: A New Homeostatic Network? 197
10.6.1 Signalling Actions of Host Heat Shock Proteins 198
10.7 Bacterial Heat Shock Proteins Are Virulence Factors? 198
10.7.1 Bacterial Molecular Chaperones Act as Bacterial Adhesins 199
10.7.2 Bacterial Molecular Chaperones as Directly Acting Virulence Factors 200
10.8 Bacterial Molecular Chaperones as Therapeutic Targets 206
10.9 Conclusions 207
11 Membrane-Expressed and Extracellular Stress Proteins in Infectious Disease 216
11.1 Heat Shock Proteins (HSPs) 216
11.2 Membrane-Expressed and Extracellular Heat Shock Proteins Elicit Immune Responses 217
11.3 Microbial Infections 220
11.3.1 Escherichia coli ( E. coli ) 221
11.3.2 Salmonella typhimurium 221
11.3.3 Helicobacter pylori 221
11.3.4 Chlamydia pneumonia and Chlamydia trachomatis 222
11.3.5 Human Immunodeficiency Virus (HIV) 222
11.3.6 Epstein-Barr Virus (EBV) 223
11.3.7 Measles 224
12 Circulating Stress Proteins in Infectious Disease 231
12.1 Introduction 231
12.2 Increase of Circulating Heat Shock Proteins During Infection 233
12.3 Origin of Circulating Heat Shock Proteins 234
12.4 Role of Circulating Heat Shock Proteins in Infection 235
12.5 Measurement of Circulating Heat Shock Proteins 236
12.6 Clinical Utility of Circulating Heat Shock Proteins Determinations 237
12.7 Conclusion 238
13 Heat Shock Proteins, Genital Tract Infections and Reproductive Outcome 244
13.1 Infection-Related Heat Shock Protein Expression in the Female Genital Tract 245
13.1.1 Chlamydia trachomatis Infection 246
13.1.2 Vaginal Infections 246
13.1.3 Congenital Cytomegalovirus (CMV) Infection 247
13.2 Heat Shock Protein Expression During Pregnancy 247
13.2.1 Preimplantation Heat Shock Protein Expression 248
13.2.2 Influence of Antibodies to Heat Shock Proteins on Pre-implantation Embryo Development 248
13.2.3 Antibodies to Heat Shock Proteins and In Vitro Fertilisation 249
13.2.4 Heat Shock Proteins in Amniotic Fluid 250
13.2.5 Heat Shock Proteins as Biomarkers of Adverse Pregnancy Events 251
13.3 Polymorphisms in Heat Shock Protein Genes Influencing Pregnancy Outcome 253
13.4 Conclusions 255
14 Heat Shock Proteins and Oral Diseases: Special Focuson Periodontitis 260
14.1 Gingivitis and Periodontitis 260
14.1.1 Etiology and Pathology 261
14.1.1.1 Gingivitis 261
14.1.1.2 Periodontitis 261
14.2 Heat Shock Proteins 262
14.2.1 Heat Shock Proteins and Atherosclerosis 263
14.2.2 Heat-Shock Proteins and Temporomandibular Joint Disorders 264
14.2.3 Heat Shock Proteins and Oral Mucosal Lesions 264
14.2.3.1 Oral Lichen 264
15 Temperature Matters: Cellular Targets of Hyperthermia in Cancer Biology and Immunology 270
15.1 Introduction 271
15.2 Hyperthermia as a Radiosensitizer 271
15.3 Heat Shock Temperatures (4245C): Effects on Cell Structure and Morphology and the Plasma Membrane 274
15.3.1 Changes in Membrane Fluidity and Surface Morphology 274
15.3.2 Changes in Cytoskeletal Properties 278
15.3.3 Changes in Membrane Potential and Permeability 279
15.3.4 Changes in Plasma Membrane Association of Heat Shock and Other Proteins 280
15.3.5 Changes in Membrane Lipid Composition 282
15.4 Mild Hyperthermia (3941C): Effects on Tumor and Immune Cells 283
15.4.1 Effects on the Tumor 286
15.4.1.1 Changes in Tumor Oxygenation 286
15.4.1.2 Changes in Protein Expression by Tumor Cells 287
15.4.2 Effects on Immune Cells 287
15.4.2.1 Effects on Lymphocytes 288
15.4.2.2 Effects on Natural Killer Cell Functions 289
15.4.2.3 Effects on Macrophage Functions 291
15.4.2.4 Effects on Dendritic Cell Morphology and Function 292
15.5 Fever Range Hyperthermia: Effects on the Plasma Membrane 294
15.5.1 Plasma Membrane Lateral Compartmentalization: Lipid Rafts 294
15.5.2 Mild Hyperthermia Effects on Lipid Raft Organization 296
15.6 Conclusions 299
15.7 Critical Questions for Future Research 301
Index 310