| Preface | 6 |
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| Contents | 8 |
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| The Varicella-Zoster Virus Genome | 16 |
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| 1 Genome Structure and Organization | 17 |
| 1.1 VZV Genome | 17 |
| 1.2 VZV Genes | 18 |
| 1.2.1 VZV Immediate-Early Genes | 18 |
| 1.2.2 VZV Genes Encoding Replication Proteins | 18 |
| 1.2.3 VZV Genes Encoding Putative Late Proteins | 20 |
| 1.2.4 VZV Genes Encoding Glycoproteins | 20 |
| 2 Comparative Genomics of VZV and HSV | 21 |
| 2.1 Core Proteins Conserved with Herpesviruses in Other Subfamilies | 21 |
| 2.2 VZV Functional and Nonfunctional Homologs of HSV Genes | 21 |
| 2.3 VZV Genes Not Conserved with HSV | 21 |
| 2.4 HSV Genes Not Conserved with VZV | 22 |
| 3 Mutagenesis with Cosmids and BACs | 22 |
| 3.1 Mutagenesis Using Marker Rescue | 22 |
| 3.2 Mutagenesis Using Cosmids | 22 |
| 3.3 Mutagenesis Using BACs | 23 |
| 3.4 Results of Mutagenesis Studies | 23 |
| 3.5 VZV as an Expression Vector | 25 |
| 3.6 Use of Genetics to Develop Safer VZV Vaccines | 26 |
| References | 26 |
| VZV Molecular Epidemiology | 30 |
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| 1 Introduction | 31 |
| 1.1 What is Molecular Epidemiology? | 31 |
| 1.2 VZV Molecular Epidemiology: The Historical Context | 31 |
| 2 Genetic Variation in VZV: Tools for Molecular Epidemiology | 32 |
| 2.1 Restriction Fragment Length Polymorphisms | 32 |
| 2.2 Length Polymorphisms of Variable Regions | 34 |
| 2.3 Restriction Site Polymorphisms: BglI and PstI Digests | 35 |
| 2.4 Single Nucleotide Polymorphisms | 36 |
| 2.5 Genome Sequencing | 41 |
| 3 Molecular Epidemiology in Practice | 41 |
| 3.1 Varicella-Zoster Virus Evolution and Clades | 41 |
| 3.1.1 Mutation and Evolution of VZV | 42 |
| 3.1.2 Recombination and VZV Evolution | 43 |
| 3.1.3 Reconstructing the Evolutionary History of VZV | 43 |
| 3.2 Geographical Spread of VZV Strains | 44 |
| 3.3 Molecular Epidemiology and VZV Pathogenesis | 47 |
| 3.3.1 Genotyping, Reinfection, and Reactivation | 47 |
| 3.3.2 Genotyping and Virulence | 48 |
| 3.4 Molecular Epidemiology Transmission and Infection Control | 49 |
| 3.5 Molecular Epidemiology of VZV Outbreaks | 50 |
| 3.5.1 Molecular Epidemiology and Public Health | 51 |
| 4 Summary | 52 |
| References | 52 |
| Roles of Cellular Transcription Factors in VZV Replication | 58 |
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| 1 Introduction | 59 |
| 2 Role of the Eukaryotic Mediator Complex in IE62-Directed Transcriptional Activation | 60 |
| 2.1 Mediator | 61 |
| 2.2 Physical and Functional Interaction Between Mediator and IE62 | 62 |
| 2.3 Mapping of the Minimal IE62 TAD | 64 |
| 2.4 The IE62 TAD Interacts Directly with MED25 | 64 |
| 2.5 The IE62 TAD Is Unstructured in the Absence of a Binding Partner | 65 |
| 2.6 Future Directions | 66 |
| 3 Mechanisms of Activation of the ORF62 Promoter | 67 |
| 3.1 HCF-1 | 67 |
| 3.2 HCF-1 and Chromatin Remodeling | 68 |
| 3.3 Future Directions | 69 |
| 4 Cellular Transcription Factors and Origin-Dependent DNA Replication | 70 |
| 4.1 Interaction of Transcription Factors with the Downstream Region of oriS | 72 |
| 4.2 The Sp1/Sp3 Site Is Involved in Origin-Dependent DNA Replication | 73 |
| 4.3 Future Directions | 73 |
| 5 Summary | 74 |
| References | 74 |
| Effects of Varicella-Zoster Virus on Cell Cycle Regulatory Pathways | 81 |
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| 1 Introduction | 82 |
| 1.1 VZV Tropism for Nondividing Cells | 82 |
| 1.2 Characterization of the Cell Cycle in VZV Host Cells | 83 |
| 1.3 VZV Dysregulates the Cell Cycle in Human Foreskin Fibroblasts | 85 |
| 1.4 Virus and Host DNA Synthesis in VZV-Infected Human Foreskin Fibroblasts | 86 |
| 1.5 Concluding Remarks | 89 |
| References | 89 |
| Varicella-Zoster Virus Open Reading Frame 66 Protein Kinase and Its Relationship to Alphaherpesvirus US3 Kinases | 92 |
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| 1 Introduction | 93 |
| 2 Genetics | 93 |
| 3 ORF66 Structure and Characteristics | 94 |
| 4 ORF66 Targets | 96 |
| 4.1 Autophosphorylation | 96 |
| 4.2 IE62 | 98 |
| 4.3 Matrin 3 | 99 |
| 4.4 Histone Deacetylases | 100 |
| 5 Cellular and Viral Activities Modulated by the ORF66 Protein Kinase | 101 |
| 5.1 MHC-I Surface Presentation | 101 |
| 5.2 IFN Signaling | 102 |
| 5.3 Apoptosis | 103 |
| 6 Alphaherpesvirus US3 Kinase Studies that Guide the Search for Roles of ORF66 | 103 |
| 6.1 US3 Kinases and Inhibition of Apoptosis | 104 |
| 6.2 US3 Modulation of HDAC | 104 |
| 6.3 Nucleocapsid Egress | 105 |
| 6.4 Alteration of the Host Cytoskeleton | 106 |
| 7 Concluding Remarks | 107 |
| References | 107 |
| VZV ORF47 Serine Protein Kinase and Its Viral Substrates | 112 |
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| 1 Introduction | 113 |
| 2 Molecular Evolution of VZV and OR
|