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Human Cytomegalovirus

:	Thomas E. Shenk, Mark F. Stinski
:	Thomas E. Shenk, Mark F. Stinski
:	Human Cytomegalovirus
:	Springer-Verlag
:	9783540773498
:	1
:	CHF 190.80
:

:	Mikrobiologie
:	English

:	479
:	Wasserzeichen/DRM
:	PC/MAC/eReader/Tablet
:	PDF

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.

	Preface	5
	Contents	7
	Contributors	9
	Human Cytomegalovirus Genome	14
	Introduction	15
	Genome Organization and cis -Acting Elements	16
	Clinical Isolates and Laboratory Strains	17
	Protein-Coding ORFs	19
	Genomic Organization: Evolution and Function	29
	Perspectives	30
	References	30
	Human Cytomegalovirus microRNAs	34
	Introduction	35
	miRNA Biogenesis	36
	Location and Conservation of HCMV miRNAs	40
	HCMV miRNA Expression	44
	Potential Function of HCMV miRNAs	47
	Future Directions	48
	References	48
	Mutagenesis of the Cytomegalovirus Genome	54
	Introduction	55
	CMV Genetics in Cells	55
	CMV Genetics in Bacteria	58
	Genetic Analysis of Essential Genes	66
	Concluding Remarks	70
	References	70
	Cytomegalovirus Cell Tropism	76
	Target Cells of HCMV Infection	77
	Pathogenetic Role of Selected Cell Types	81
	Cell Biological Basis of HCMV Cell Tropism	86
	Cell Tropism of Other Cytomegaloviruses	89
	Impact of Cell Tropism Analyses	90
	References	91
	Virus Entry and Innate Immune Activation	98
	Introduction to Virus Entry	99
	Cellular Receptors Proposed for HCMV Entry	99
	Envelope and Membrane Fusion	103
	Introduction to Activation of Innate Immunity	104
	Activation of Inflammatory Cytokines	104
	Activation of Interferon Responses	106
	Coordination of Entry Events and Innate Immune Activation Steps	107
	Perspectives	109
	References	109
	Functions of Human Cytomegalovirus Tegument Proteins Prior to Immediate Early Gene Expression	114
	Introduction	114
	Tegument Proteins Known to Act at the Very Start of HCMV Infection	117
	Delivery of the Genome to the Nucleus	118
	Initiating Viral IE Gene Expression	120
	Model for Postfusion, Preimmediate Early Events	123
	Perspectives	124
	References	125
	Initiation of Cytomegalovirus Infection at ND10	130
	Structural Observations in the First Hours After CMV Infection and Their Limits in Interpretative Value	131
	Are ND10 Really the Start Sites of CMV Transcription?	134
	Structural and Functional Aspects of IE1	135
	IE1 Counteracts the Host Cell s Silencing Mechanisms	136
	Effect of ND10-Associated Proteins on CMV	138
	Perspectives	141
	References	142
	Functional Roles of the Human Cytomegalovirus Essential IE86 Protein	146
	Introduction	146
	Mapping the Functional Domains of the IE86 Protein	148
	Autoregulation of the MIE Promoter	152
	Transcription from Viral and Cellular Promoters	153
	Cell Cycle Progression	155
	Perspectives	158
	References	159
	Nuts and Bolts of Human Cytomegalovirus Lytic DNA Replication	166
	Introduction	167
	Essential Region I: IE2-UL84 Responsive Promoter in oriLyt	168
	Essential Region II: RNA/DNA Hybrid Structure	171
	Viral-Encoded trans -Acting Factors Required for Lytic Replication	172
	UL84 and IE2	174
	Viral and Cellular Encoded UL84 Binding Partners	175
	Summary and Perspectives	176
	References	176
	Interactions of Human Cytomegalovirus Proteins with the Nuclear Transport Machinery	180
	Introduction	181
	Nuclear Import and Export Pathways	182
	Interaction of the Human Cytomegalovirus Protein pUL69 with the mRNA Export Factor UAP56	186
	RNA Export by pUL69	189
	Interaction of the HCMV pUL84 with Importin-a Proteins	191
	Unconventional Interactions with the Nuclear Transport Machinery: Novel Targets for Antiviral Strategies?	192
	References	193
	Structure and Formation of the Cytomegalovirus Virion	200
	Introduction	200
	Formation of the Nucleocapsid	203
	Tegumentation and Envelopment	209
	Concluding Thoughts	212
	References	212
	Human Cytomegalovirus Modulation of Signal Transduction	218
	Introduction	219
	Signaling Overview	220
	Biological Rationale for Modulation of Host Cell Signaling	225
	Role of Signaling in Pathogenesis	228
	Final Thoughts	228
	References	229
	Chemokines and Chemokine Receptors Encoded by Cytomegaloviruses	234
	Introduction	235
	Evolution of CMV vCK Genes	236
	Chemokine Receptors Encoded by CMVs	240
	Perspectives	250
	References	250
	Subversion of Cell Cycle Regulatory Pathways	256
	The Host Cell Cycle	256
	The Effect of HCMV on the Cell Cycle	259
	Importance of Subversion of the Cell Cycle for the Viral Infection	261
	Perspectives	269
	References	270
	Modulation of Host Cell Stress Responses by Human Cytomegalovirus	276
	Introduction	277
	Background: PI3K-Akt-TSC-mTOR Signaling	278
	Background: The Complexes of mTOR Kinase and Their Activities	279
	HCMV and the Activation of the PI3K-Akt-TSC-mTORC1 Pathway	281
	The Effects of HCMV Downstream of Akt	284
	HCMV Effects on the mTOR Complexes and Their Substrates	285
	HCMV Effects on eIF4E and Mnk-1	286
	Conclusions, Questions, Speculations	287
	References	289
	Control of Apoptosis by Human Cytomegalovirus	294
	Introduction	295
	vMIA Controls Mitochondria-Dependent Death	296
	vICA Controls Caspase-8	300
	IE1 491aa , IE2 579aa , and Akt-Dependent Pro-survival Pathways	300
	UL38 Decreases Intrinsic Stress	301
	M45 Is a Cell Type-Specific Survival Factor	302
	m41, Late Infection, and the Golgi Apparatus	303
	ß2.7 and Mitochondrial Respiratory Complex I	303
	Summary and Perspectives	303
	References	304
	Aspects of Human Cytomegalovirus Latency and Reactivation	310
	Introduction	311
	Latency, Carriage and Reactivation of HCMV in the Cells of the Myeloid Lineage	311
	Models of HCMV Latency Using Experimental Infection	313
	Viral Gene Expression Associated with HCMV Latency	314
	Key Aspects of HCMV Latency and Reactivation	315
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