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;22