Shenk / Stinski Human Cytomegalovirus

1. Auflage 2008
ISBN: 978-3-540-77349-8
Verlag: Springer Berlin Heidelberg
Format: PDF
Kopierschutz: 1 - PDF Watermark

E-Book, Englisch, Band 325, 479 Seiten

Reihe: Current Topics in Microbiology and Immunology

This volume has gathered some of the experts in the field to review aspects of our understanding of CMV and to offer perspectives of the current problems associated with CMV. The editors and authors hope that the chapters will lead to a better understanding of the virus that will assist in the development of new and unique antivirals, a protective vaccine, and a full understanding of CMV's involvement in human disease.

Autoren/Hrsg.

Shenk, Thomas E.

Stinski, Mark F.

Inhaltsverzeichnis

1;Preface;5
2;Contents;7
3;Contributors;9
4;Human Cytomegalovirus Genome;14
4.1;Introduction;15
4.2;Genome Organization and cis -Acting Elements;16
4.3;Clinical Isolates and Laboratory Strains;17
4.4;Protein-Coding ORFs;19
4.5;Genomic Organization: Evolution and Function;29
4.6;Perspectives;30
4.7;References;30
5;Human Cytomegalovirus microRNAs;34
5.1;Introduction;35
5.2;miRNA Biogenesis;36
5.3;Location and Conservation of HCMV miRNAs;40
5.4;HCMV miRNA Expression;44
5.5;Potential Function of HCMV miRNAs;47
5.6;Future Directions;48
5.7;References;48
6;Mutagenesis of the Cytomegalovirus Genome;54
6.1;Introduction;55
6.2;CMV Genetics in Cells;55
6.3;CMV Genetics in Bacteria;58
6.4;Genetic Analysis of Essential Genes;66
6.5;Concluding Remarks;70
6.6;References;70
7;Cytomegalovirus Cell Tropism;76
7.1;Target Cells of HCMV Infection;77
7.2;Pathogenetic Role of Selected Cell Types;81
7.3;Cell Biological Basis of HCMV Cell Tropism;86
7.4;Cell Tropism of Other Cytomegaloviruses;89
7.5;Impact of Cell Tropism Analyses;90
7.6;References;91
8;Virus Entry and Innate Immune Activation;98
8.1;Introduction to Virus Entry;99
8.2;Cellular Receptors Proposed for HCMV Entry;99
8.3;Envelope and Membrane Fusion;103
8.4;Introduction to Activation of Innate Immunity;104
8.5;Activation of Inflammatory Cytokines;104
8.6;Activation of Interferon Responses;106
8.7;Coordination of Entry Events and Innate Immune Activation Steps;107
8.8;Perspectives;109
8.9;References;109
9;Functions of Human Cytomegalovirus Tegument Proteins Prior to Immediate Early Gene Expression;114
9.1;Introduction;114
9.2;Tegument Proteins Known to Act at the Very Start of HCMV Infection;117
9.3;Delivery of the Genome to the Nucleus;118
9.4;Initiating Viral IE Gene Expression;120
9.5;Model for Postfusion, Preimmediate Early Events;123
9.6;Perspectives;124
9.7;References;125
10;Initiation of Cytomegalovirus Infection at ND10;130
10.1;Structural Observations in the First Hours After CMV Infection and Their Limits in Interpretative Value;131
10.2;Are ND10 Really the Start Sites of CMV Transcription?;134
10.3;Structural and Functional Aspects of IE1;135
10.4;IE1 Counteracts the Host Cell’s Silencing Mechanisms;136
10.5;Effect of ND10-Associated Proteins on CMV;138
10.6;Perspectives;141
10.7;References;142
11;Functional Roles of the Human Cytomegalovirus Essential IE86 Protein;146
11.1;Introduction;146
11.2;Mapping the Functional Domains of the IE86 Protein;148
11.3;Autoregulation of the MIE Promoter;152
11.4;Transcription from Viral and Cellular Promoters;153
11.5;Cell Cycle Progression;155
11.6;Perspectives;158
11.7;References;159
12;Nuts and Bolts of Human Cytomegalovirus Lytic DNA Replication;166
12.1;Introduction;167
12.2;Essential Region I: IE2-UL84 Responsive Promoter in oriLyt;168
12.3;Essential Region II: RNA/DNA Hybrid Structure;171
12.4;Viral-Encoded trans -Acting Factors Required for Lytic Replication;172
12.5;UL84 and IE2;174
12.6;Viral and Cellular Encoded UL84 Binding Partners;175
12.7;Summary and Perspectives;176
12.8;References;176
13;Interactions of Human Cytomegalovirus Proteins with the Nuclear Transport Machinery;180
13.1;Introduction;181
13.2;Nuclear Import and Export Pathways;182
13.3;Interaction of the Human Cytomegalovirus Protein pUL69 with the mRNA Export Factor UAP56;186
13.4;RNA Export by pUL69;189
13.5;Interaction of the HCMV pUL84 with Importin-a Proteins;191
13.6;Unconventional Interactions with the Nuclear Transport Machinery: Novel Targets for Antiviral Strategies?;192
13.7;References;193
14;Structure and Formation of the Cytomegalovirus Virion;200
14.1;Introduction;200
14.2;Formation of the Nucleocapsid;203
14.3;Tegumentation and Envelopment;209
14.4;Concluding Thoughts;212
14.5;References;212
15;Human Cytomegalovirus Modulation of Signal Transduction;218
15.1;Introduction;219
15.2;Signaling Overview;220
15.3;Biological Rationale for Modulation of Host Cell Signaling;225
15.4;Role of Signaling in Pathogenesis;228
15.5;Final Thoughts;228
15.6;References;229
16;Chemokines and Chemokine Receptors Encoded by Cytomegaloviruses;234
16.1;Introduction;235
16.2;Evolution of CMV vCK Genes;236
16.3;Chemokine Receptors Encoded by CMVs;240
16.4;Perspectives;250
16.5;References;250
17;Subversion of Cell Cycle Regulatory Pathways;256
17.1;The Host Cell Cycle;256
17.2;The Effect of HCMV on the Cell Cycle;259
17.3;Importance of Subversion of the Cell Cycle for the Viral Infection;261
17.4;Perspectives;269
17.5;References;270
18;Modulation of Host Cell Stress Responses by Human Cytomegalovirus;276
18.1;Introduction;277
18.2;Background: PI3K-Akt-TSC-mTOR Signaling;278
18.3;Background: The Complexes of mTOR Kinase and Their Activities;279
18.4;HCMV and the Activation of the PI3K-Akt-TSC-mTORC1 Pathway;281
18.5;The Effects of HCMV Downstream of Akt;284
18.6;HCMV Effects on the mTOR Complexes and Their Substrates;285
18.7;HCMV Effects on eIF4E and Mnk-1;286
18.8;Conclusions, Questions, Speculations;287
18.9;References;289
19;Control of Apoptosis by Human Cytomegalovirus;294
19.1;Introduction;295
19.2;vMIA Controls Mitochondria-Dependent Death;296
19.3;vICA Controls Caspase-8;300
19.4;IE1 491aa , IE2 579aa , and Akt-Dependent Pro-survival Pathways;300
19.5;UL38 Decreases Intrinsic Stress;301
19.6;M45 Is a Cell Type-Specific Survival Factor;302
19.7;m41, Late Infection, and the Golgi Apparatus;303
19.8;ß2.7 and Mitochondrial Respiratory Complex I;303
19.9;Summary and Perspectives;303
19.10;References;304
20;Aspects of Human Cytomegalovirus Latency and Reactivation;310
20.1;Introduction;311
20.2;Latency, Carriage and Reactivation of HCMV in the Cells of the Myeloid Lineage;311
20.3;Models of HCMV Latency Using Experimental Infection;313
20.4;Viral Gene Expression Associated with HCMV Latency;314
20.5;Key Aspects of HCMV Latency and Reactivation;315
20.6;Other Sites of HCMV Latency;321
20.7;Conclusion;322
20.8;References;322
21;Murine Model of Cytomegalovirus Latency and Reactivation;328
21.1;Introduction;329
21.2;Definitions and Caveats: The Difference Between Latency and Persistence;330
21.3;Latent Viral Genome Load Defining the Risk of Recurrence;333
21.4;Bidirectional Gene Pair Architecture of the Regulatory Major Immediate Early Locus;334
21.5;Stochastic Desilencing of the Major Immediate Early Locus During Latency;336
21.6;Extrinsic Signals Triggering Transcriptional Reactivation and Recurrence;336
21.7;Role of Viral Chromatin Remodeling;337
21.8;Dynamic Control of Latency at Immunological Checkpoints: The Immune Sensing Hypothesis;338
21.9;Concluding Thoughts and Perspectives;341
21.10;References;341
22;Cytomegalovirus Immune Evasion;346
22.1;The Type I Interferon System and Its Effects on CMV Replication;347
22.2;Interference with Antigen Presentation by Cytomegalovirus;350
22.3;Escaping the Natural Killer Cell Response;355
22.4;Perspectives;361
22.5;References;362
23;Cytomegalovirus Vaccine Development;374
23.1;Spectrum of HCMV Disease, Rationale for Vaccine, and Target Population;375
23.2;Evidence That Immunity Protects Against HCMV Infection and Disease;378
23.3;HCMV Vaccines in Clinical Trials;380
23.4;HCMV Vaccine Approaches in Preclinical Development;385
23.5;Perspectives;390
23.6;References;391
24;Cytomegalovirus Infection in the Human Placenta: Maternal Immunity and Developmentally Regulated Receptors on Trophoblasts Converge;396
24.1;Introduction;397
24.2;Spatially Distinct Infection in the Developing Placenta;397
24.3;Villous Cytotrophoblasts Express EGFRand Upregulate Integrin aV;399
24.4;Cell Column Cytotrophoblasts Induce Integrin;401
24.5;Expression;401
24.6;Replication in Differentiating/Invading Cytotrophoblasts;402
24.7;Infection Impairs Cell Functions Through Diverse Membrane Proximal Events;404
24.8;Implications for Congenital CMV Infection;405
24.9;References;406
25;Mechanisms of Cytomegalovirus-Accelerated Vascular Disease: Induction of Paracrine Factors That Promote Angiogenesis and Wound Healing;410
25.1;Introduction;411
25.2;Tissue Repair and Angiogenic Factors Mediate TVS;411
25.3;Animal Models of CMV-Accelerated Graft Rejection;413
25.4;In Vitro Models of HCMV-Mediated Wound Healing and Angiogenesis;415
25.5;Conclusions;424
25.6;References;425
26;Manifestations of Human Cytomegalovirus Infection: Proposed Mechanisms of Acute and Chronic Disease;430
26.1;Introduction;431
26.2;Natural History of Acute CMV Infections in the Normal Host;434
26.3;Natural History of Acute CMV Infection in the Immunocompromised Host;439
26.4;Diseases Associated with Chronic Infection;455
26.5;References;462
27;Index;484