This comprehensive account of the human herpesviruses provides an encyclopedic overview of their basic virology and clinical manifestations. This group of viruses includes human simplex type 1 and 2, Epstein–Barr virus, Kaposi’s Sarcoma-associated herpesvirus, cytom-egalovirus, HHV6A, 6B, and 7, and varicella-zoster virus. The viral diseases and cancers they cause are significant and often recurrent. Their prevalence in the developed world accounts for a major burden of disease, and as a result there is a great deal of research into the pathophysiology of infection and immunobiology. Another important area covered within this volume concerns antiviral therapy and the development of vaccines. All these aspects are covered in depth, both scientifically and in terms of clinical guidelines for patient care. The text is illustrated generously throughout and is fully referenced to the latest research and developments.

Contents

• Contributors
• Preface
• I. Introduction: definition and classification of the human herpesviruses
  Editor: Bernard Roizman.
  • 1. Overview of classification
    Andrew J. Davison.
    • Introduction
    • Morphological criteria
    • Serological criteria
    • Biological criteria
    • Genomic criteria
    • Species definition
    • Acknowledgment
    • References
  • 2. Comparative analysis of the genomes
    Andrew J. Davison.
    • Introduction
    • Genome structures
    • Genome sequences
    • Gene content
    • Genome comparisons and evolution
    • Outlook
    • Acknowledgment
    • References
  • 3. Comparative virion structures of human herpesviruses
    Fenyong Liu and Z. Hong Zhou.
    • Introduction
    • Different virus-related particles found in infected cells
    • Compositions and three-dimensional structural comparisons of alpha, beta and gammaherpesvirus capsids
    • Structure and packaging of viral genomic DNA
    • Structure and assembly of tegument
    • Structure and assembly of viral envelope
    • Other constituents in the virions
    • Acknowledgments
    • References
  • 4. Comparative analysis of herpesvirus-common proteins
    Edward S. Mocarski Jr.
    • Introduction
    • Virion structural proteins
    • Entry into host cells
    • Regulation of gene expression and replication
    • Viral DNA synthesis and nucleotide metabolism
    • Capsid assembly and DNA encapsidation
    • Maturation
    • References
• II.1. Basic virology and viral gene effects on host cell functions: alphaherpesviruses
  Editors: Gabriella Campadelli-Fiume and Bernard Roizman.
  • 5. Genetic comparison of human alphaherpesvirus genomes
    Joel D. Baines and Philip E. Pellett.
    • VZV genes that are absent from HSV genomes
    • L component genes unique to the simplexviruses
    • S component genes unique to the human simplexviruses
    • References
  • 6. Alphaherpes viral genes and their functions
    Bernard Roizman and Gabriella Campadelli-Fiume.
    • Introduction
    • Acknowledgments
    • References
  • 7. Entry of alphaherpesviruses into the cell
    Gabriella Campadelli-Fiume and Laura Menotti.
    • Introduction
    • The membrane proteins
    • HSV
    • VZV
    • Acknowledgments
    • References
  • 8. Early events pre-initiation of alphaherpes viral gene expression
    Thomas M. Kristie.
    • The HSV IE regulatory domains: multiple sites for differential regulation
    • The assembly of the HSV IE enhancer core complex
    • Ancillary factors: Sp1 and GABP
    • VZV IE gene expression: parallels and divergence
    • Regulation of the IE genes: multiple levels and response potentials
    • The regulation of the IE genes: reactivation of HSV from the latent state
    • Questions and future directions
    • Acknowledgments
    • References
  • 9. Initiation of transcription and RNA synthesis, processing and transport in HSV and VZV infected cells
    Rozanne M. Sandri-Goldin.
    • Initiation of transcription and RNA synthesis
    • RNA processing and transport
    • Concluding remarks
    • References
  • 10. Alphaherpesvirus DNA replication
    John Hay and William T. Ruyechan.
    • Structure of the genome
    • The origins of DNA replication
    • Location of DNA synthesis
    • Proteins involved in DNA synthesis
    • DNA replication and the cell cycle
    • Maturation and packaging of viral DNA
    • Recombination
    • Latency
    • Future directions
    • References
  • 11. Envelopment of herpes simplex virus nucleocapsids at the inner nuclear membrane
    Joel D. Baines.
    • Introduction
    • Anatomy of the nuclear membrane: it’s all connected
    • References
  • 12. The egress of alphaherpesviruses from the cell
    Gabriella Campadelli-Fiume.
    • HSV
    • Cell-to-cell spread
    • Acknowledgments
    • References
  • 13. The strategy of herpes simplex virus replication and takeover of the host cell
    Bernard Roizman and Brunella Taddeo.
    • Introduction
    • Gene content, organization, and fundamental design of the viral genome
    • Mobilization of cellular proteins for enhanced replication of HSV
    • The objectives and general strategy of anti-host functions
    • The activation of NF-κB
    • Degradation of mRNA in infected cells
    • Specific degradation of cellular proteins in wild-type virus-infected cells
    • Shut down of the interferon pathways to host resistance to infection
    • HSV blocks pro-apoptotic cellular functions
    • Conclusions
    • Acknowledgments
    • References
• II.2. Basic virology and viral gene effects on host cell functions: betaherpesviruses
  Editor: Edward Mocarski.
  • 14. Comparative genome and virion structure
    Andrew J. Davison and David Bhella.
    • Introduction
    • Genome structures
    • Genes
    • Virion structure
    • References
  • 15. Betaherpes viral genes and their functions
    E. S. Mocarski Jr.
    • Introduction
    • Virion structural proteins
    • Entry into host cells
    • Regulation of gene expression and replication
    • Viral DNA synthesis and nucleotide metabolism
    • Capsid assembly and DNA encapsidation
    • Maturation
    • Latency
    • References
  • 16. Early events in human cytomegalovirus infection
    Teresa Compton and Adam Feire.
    • Introduction
    • Cellular receptors for HCMV
    • Entry activated cell signaling
    • Cellular integrins may serve as coreceptors for betaherpesviruses
    • Activation of innate immunity during entry
    • Roles of betaherpesvirus envelope glycoproteins in virus entry
    • Coordination of entry and innate immune activation
    • References
  • 17. Immediate–early viral gene regulation and function
    Mark F. Stinski and Jeffery L. Meier.
    • Introduction
    • Betaherpesvirus immediate early genes
    • Betaherpesvirus transcriptional enhancers upstream of the MIE genes
    • Function of the betaherpesvirus major immediate–early enhancers
    • Silencing of the immediate-early genes
    • Reactivation of the immediate–early genes
    • Betaherpesvirus major immediate–early genes
    • Functions of the major immediate–early viral proteins
    • Factors that stimulate betaherpesvirus immediate–early gene expression
    • Infection and dysregulation of the cell cycle by betaherpesviruses
    • Summary
    • Acknowledgments
    • References
  • 18. Early viral gene expression and function
    Elizabeth A. White and Deborah H. Spector.
    • Introduction
    • Identification of HCMV early genes
    • HCMV-mediated changes in the cellular environment prior to early gene expression
    • Functions of viral early genes
    • Transactivating functions of the major IE proteins
    • Additional immediate early proteins have regulatory roles
    • UL112–113 transcription is differentially controlled at early and late times
    • Multiple cis-acting sequences regulate UL54 expression
    • UL4 expression is controlled at the transcriptional and translational levels
    • Human herpesviruses 6 and 7
    • Conclusions
    • References
  • 19. DNA synthesis and late viral gene expression
    David G. Anders, Julie A. Kerry, and Gregory S. Pari.
    • Overview
    • Betaherpesvirus replication proteins
    • Betaherpesvirus replication origins
    • Late gene expression
    • References
  • 20. Maturation and egress
    Bill Britt.
    • Introduction
    • References
  • 21. Viral modulation of the host response to infection
    A. Louise McCormick and Edward S. Mocarski Jr.
    • Modulation of histone deacetylase activity
    • Modulation of IRF –3
    • Activation of NK -κB and interferon response genes
    • Impact on the host cell cycle
    • Suppression of apoptosis
    • vMIA (pUL37×1)
    • vICA (pUL36)
    • Other cell death suppressors
    • Alteration of extrinsic cell death pathways during infection
    • Summary
    • References
• II.3. Basic virology and viral gene effects on host cell functions: gammaherpesviruses
  Editor: Patrick S. Moore.
  • 22. Introduction to the human γ-herpesviruses
    Richard Longnecker and Frank Neipel.
    • Introduction
    • The γ-herpesvirus family
    • The discovery of Epstein–Barr virus (EBV)
    • Human disease associated with EBV infection
    • EBV life cycle
    • The discovery of Kaposi’s sarcoma-associated herpesvirus (KSHV)
    • KSHV life cycle
    • Human disease associated with KSHV infection
    • Phylogenetic relationship between EBV, KSHV, and non-human γ-herpesvirus genomes
    • Human γ-herpesviruses genomes
    • Characteristics of the γ-herpesvirus virion
    • Conclusions
    • Acknowledgments
    • General historical reading
    • References
  • 23. Gammaherpesviruses entry and early events during infection
    Bala Chandran and Lindsey Hutt-Fletcher.
    • Target cells for EBV
    • Target cells for KSHV
    • Virion structure
    • Virus structural proteins involved in entry
    • Virus attachment
    • Penetration
    • Cell surface signaling during entry
    • Cytoplasmic trafficking, delivery of viral genome into the nucleus
    • Summary
    • References
  • 24. Maintenance and replication during latency
    Paul M. Lieberman, Jianhong Hu, and Rolf Renne.
    • Introduction
    • EBV (lymphocryptovirus)
    • Properties of the episomal latent viral genome
    • Chromatin organization of the latent episome
    • DNA methylation of latent EBV
    • Molecular biology of OriP
    • Properties of EBNA 1
    • Cellular proteins that interact with EBNA 1
    • Cellular proteins that interact with OriP
    • Mechanism of OriP- DNA replication
    • Mechanism of viral chromosome replication
    • Mechanisms of plasmid segregation
    • KSHV (Rhadinovirus)
    • The KSHV episome in latently infected cells
    • Properties of the latency-associated nuclear antigen (LANA)
    • Latent DNA replication and segregation
    • Summary
    • References
  • 25. Reactivation and lytic replication of EBV
    Shannon C. Kenney.
    • Viral pathogenesis
    • Activation of lytic EBV infection
    • EBV immediate-early proteins
    • Early lytic EBV gene regulation
    • Early lytic EBV gene products
    • Viral replication
    • Late viral gene regulation
    • Late viral proteins
    • Viral assembly and egress
    • Treatment of lytic EBV infection
    • Lytic induction as a strategy for treating EBV -positive tumors
    • Unresolved issues for the future
    • Acknowledgment
    • References
  • 26. Reactivation and lytic replication of KSHV
    David M. Lukac and Yan Yuan.
    • Overview: goals of lytic replication
    • Lytic reactivation of KSHV is a critical pathogenic step in development of KS and other human diseases
    • The immune system tempers lytic reactivation of KSHV and KS development
    • MHV-68 is a model for immune control of gamma-herpesvirus reactivation from latency
    • Sites of latency and reservoirs for viral amplification in vivo
    • Primary effusion lymphoma (PEL) cells: a tissue culture model for KSHV latency and reactivation
    • Kinetic classification of KHSV lytic gene expression
    • ORF50/Rta is the viral lytic switch protein
    • Signals that control lytic reactivation of KSHV
    • Lytic replication and interactions with the host cell
    • Regulation of lytic DNA replication
    • Late genes and KSHV virion structure
    • Perspectives
    • References
  • 27. EBV gene expression and regulation
    Lawrence S. Young, John R. Arrand, and Paul G. Murray.
    • Introduction
    • Virus and genome structure
    • EBV latency in vitro and in vivo
    • Other forms of EBV latency
    • EBV replication/the lytic cascade
    • Functions and associated properties of lytic cycle gene products
    • EBV persistence in vivo
    • EBV strain variation
    • Function of the EBV latent genes: from persistence to pathology
    • EBNA1
    • EBNA2
    • EBNA3 family
    • EBNA-LP
    • LMP1
    • LMP2
    • EBERs
    • BARTs
    • MicroRNAs
    • Conclusions
    • References
  • 28. KSHV gene expression and regulation
    Thomas F. Schulz and Yuan Chang.
    • Introduction
    • Viral gene expression patterns in culture
    • Viral gene expression in vivo
    • Regulation of gene expression
    • References
  • 29. Effects on apoptosis, cell cycle and transformation, and comparative aspects of EBV with other known DNA tumor viruses
    George Klein and Ingemar Ernberg.
    • Viral strategy at the molecular level as a tumor risk factor
    • Three types of virus–host cell interactions may carry a risk
    • Early history: up and down
    • Up again, and how!
    • Classes of experimental tumor viruses
    • What does the type of virus-cell interaction tell us about tumorigenic risk?
    • EBV exploits B-cell specific regulatory mechanisms and signals
    • Growth transformation associated EBV encoded proteins
    • The latent membrane proteins (LMP) of EBV
    • EBV and Burkitt lymphoma (BL)
    • Hodgkin’s lymphoma (HL)
    • EBV and nasopharyngeal carcinoma
    • Viral expression in carcinoma cells, cell behavior and host relationships in NPC
    • Immune surveillance and the oncogenic herpesviruses – the role of immunological “anticipation”
    • Double HHV8/EBV carrying PEL cells
    • References
  • 30. KSHV manipulation of the cell cycle and apoptosis
    Patrick S. Moore.
    • Cell cycle and programmed cell death regulation
    • KSHV inhibition of apoptosis
    • Conclusions
    • References
  • 31. Human gammaherpesvirus immune evasion strategies
    Robert E. Means, Sabine M. Lang, and Jae U. Jung.
    • Introduction
    • Evasion of innate host immunity
    • Evasion of adaptive host immunity
    • Conclusions
    • References
• III.1. Pathogenesis, clinical disease, host response, and epidemiology: alphaherpes viruses
  Editors: Ann Arvin and Richard Whitley.
  • 32. Pathogenesis and disease
    Richard Whitley, David W. Kimberlin, and Charles G. Prober.
    • Pathogenesis
    • Unique biologic properties of HSV that influence pathogenesis
    • Pathology
    • Pathology of central nervous system disease
    • Impact of host response to infection on disease
    • Orolabial infection
    • Genital infection
    • Keratoconjunctivitis
    • Cutaneous infections
    • Central nervous system infections
    • Neonatal infection
    • Infection in compromised hosts
    • Acknowledgment
    • References
  • 33. Molecular basis of HSV latency and reactivation
    Chris M. Preston and Stacey Efstathiou.
    • Introduction
    • Model systems to study latency
    • The latent genome
    • The latency-associated transcripts
    • Establishment of latency
    • Maintenance of latency
    • Reactivation
    • Concluding remarks
    • Acknowledgments
    • References
  • 34. Immunobiology and host response
    David M. Koelle.
    • Introduction
    • HSV interactions with dendritic cells
    • CD8 T-cell responses to HSV
    • CD4 T-cell responses to HSV
    • T-cell costimulation and HSV
    • Antibody responses to HSV
    • Innate immunity
    • Immunomodulators and HSV
    • Chemokines
    • NK cells
    • NKT cells
    • TCRγδ cells
    • Additional interactions between HSV and the immune system
    • Summary
    • References
  • 35. Immunopathological aspects of HSV infection
    Kaustuv Banerjee and Barry T. Rouse.
    • Introduction
    • Herpes infections and ocular disease
    • Herpes simplex virus in the nervous system
    • Other possible HSV induced immune mediated conditions
    • References
  • 36. Persistence in the population: epidemiology, transmission
    Anna Wald and Lawrence Corey.
    • Epidemiology of HSV-1 and HSV-2
    • Spectrum of clinical disease
    • Immunocompetent host
    • Neonatal herpes
    • Immunocompromised persons
    • Viral shedding
    • Transmission dynamics
    • References
• III.2. Pathogenesis, clinical disease, host response, and epidemiology: alphaherpes viruses VZV
  Editors: Ann Arvin and Richard Whitley.
  • 37. VZV: pathogenesis and the disease consequences of primary infection
    Jennifer Moffat, Chia-Chi Ku, Leigh Zerboni, Marvin Sommer, and Ann Arvin.
    • Introduction
    • Systems for evaluating determinants of VZV pathogenesis in human skin and T-cells
    • Effects of VZV replication on cellular cyclin-dependent kinases and cyclins
    • Investigation of events in the pathogenesis of primary VZV infection in the SCIDhu model
    • The role of VZV glycoproteins in T-cell and skin tropism
    • Glycoprotein C
    • Glycoprotein E
    • Glycoprotein I
    • The role of regulatory proteins and viral kinases in T-cell and skin tropism
    • IE62 protein
    • IE63 protein
    • ORF64 protein
    • ORF10 protein
    • ORF47 protein
    • ORF66 protein
    • Disease consequences of primary VZV infection in healthy and immunocompromised hosts
    • Varicella in the immunocompromised host
    • Varicella in pregnancy and the newborn
    • Summary
    • References
  • 38. VZV: molecular basis of persistence (latency and reactivation)
    Jeffrey I. Cohen.
    • Site of VZV latency
    • Quantification of VZV DNA load during latency
    • Animal models for VZV latency
    • VZV transcripts expressed during latency
    • VZV proteins expressed during latency
    • Function of VZV latency-associated proteins
    • VZV genes required for establishment of latent infection
    • In vitro models for VZV latency
    • Reactivation of VZV
    • Comparison of VZV latency with that of other alphaherpesviruses
    • Is the large number of transcripts in VZV latency due to reactivation?
    • Models for VZV latency
    • VZV proteins localize to the cytoplasm, instead of the nucleus of neurons and thus are unable to carry out their activities
    • VZV proteins have different activities in neurons than in permissive cells due to differences in cellular proteins
    • Future directions
    • References
  • 39. VZV: immunobiology and host response
    Ann Arvin and Allison Abendroth.
    • Immunobiology
    • The host immune response
    • References
  • 40. VSV: persistence in the population
    Jane Seward and Aisha Jumaan.
    • Varicella: prevaccine epidemiology
    • Varicella epidemiology: post-vaccine era
    • Herpes zoster epidemiology
    • Acknowledgements
    • References
• III.3. Pathogenesis, clinical disease, host response, and epidemiology: betaherpesviruses
  Editors: Ann Arvin and Richard Whitley.
  • 41. Virus entry into host, establishment of infection, spread in host, mechanisms of tissue damage
    William Britt.
    • Introduction
    • Acquisition of HCMV: sources of virus and transmission within populations
    • Entry and spread within susceptible hosts
    • Spread within the host
    • References
  • 42. Molecular basis of persistence and latency
    Michael A. Jarvis and Jay A. Nelson.
    • Introduction
    • Summary
    • Acknowledgments
    • References
  • 43. Immunobiology and host response
    Mark R. Wills, Andrew J. Carmichael, J. H. Sinclair, and J. G. Patrick Sissons.
    • Introduction
    • References
  • 44. Persistence in the population: epidemiology and transmisson
    Suresh B. Boppana and Karen B. Fowler.
    • Introduction
    • Epidemiology of HCMV infection
    • Transmission of HCMV by mothers to infants: perinatal infections
    • Children-to-children transmission of HCMV
    • Transmission of HCMV by children to parents
    • HCMV transmission through sexual activity
    • Transmission of HCMV to child-care providers
    • Transmission of CMV in health-care settings
    • Transfusion acquired HCMV infection
    • Transplantation and HCMV infection
    • HCMV transmission from artificial insemination by donor semen
    • Summary
    • References
  • 45. HCMV persistence in the population: potential transplacental transmission
    Lenore Pereira, Ekaterina Maidji, Susan J. Fisher, Susan McDonagh, and Takako Tabata.
    • Congenital cytomegalovirus infection and the placenta
    • Placental development in early gestation
    • CMV infects the placenta in vitro and in utero
    • CMV infection dysregulates cytotrophoblast differentiation/invasion in vitro
    • References
• III.4. HHV-6A, 6B, and 7
  Editors: Ann Arvin and Richard Whitley.
  • 46. HHV-6A, 6B, and 7: pathogenesis, host response, and clinical disease
    Yasuko Mori and Koichi Yamanishi.
    • Virus entry and establishment of infection
    • Entry
    • Envelope glycoproteins for entry process
    • Spread in host, mechanisms of tissue damage
    • Effects of virus infection on host cells
    • Disease consequences
    • AIDS
    • The other possible associated diseases
    • References
  • 47. HHV-6A, 6B, and 7: molecular basis of latency and reactivation
    Kazuhiro Kondo and Koichi Yamanishi.
    • Introduction
    • Latency-associated transcripts of HHV-6
    • Gene regulation of latency-associated transcripts
    • First molecular event of HHV-6 reactivation
    • Summary
    • References
  • 48. HHV-6A, 6B, and 7: immunobiology and host response
    Fu-Zhang Wang and Philip E. Pellett.
    • Introduction
    • Cell tropism
    • Immune response
    • Virally mediated immune modulation
    • Clinical significance of immunomodulation
    • Future directions
    • References
  • 49. HHV-6A, 6B, and 7: persistence in the population, epidemiology and transmission
    Vincent C Emery and Duncan A. Clark.
    • Introduction
    • Persistence of HHV-6 and HHV-7 in individuals
    • Epidemiology of HHV-6 and HHV-7
    • HHV-6 variants A and B
    • HHV-6 and HHV-7 genotypes
    • HHV-6 integration
    • Transmission of HHV-6 and HHV-7
    • Concluding comments
    • References
• III.5. Pathogenesis, clinical disease, host response, and epidemiology: gammaherpesviruses
  Editor: Patrick S. Moore.
  • 50. Clinical and pathological aspects of EBV and KSHV infection
    Richard F. Ambinder and Ethel Cesarman.
    • EBV
    • EBV-associated tumors
    • KSHV
    • KSHV-associated angioproliferative and lymphoproliferative disorders
    • Conclusions
    • References
  • 51. EBV: immunobiology and host response
    Denis J. Moss, Scott R. Burrows, and Rajiv Khanna.
    • Introduction
    • Response during acute infection
    • Response in healthy virus carriers
    • Role of CD4+ and CD8+ CTL in control of EBV infection
    • Role of CTL effector cells in resolution of acute IM
    • T-cell receptor usage
    • Virus-driven immune modulation
    • T-cell control of EBV-associated malignancies
    • Future prospects for an EBV vaccine
    • References
  • 52. Immunobiology and host response to KSHV infection
    Dimitrios Lagos and Chris Boshoff.
    • Introduction
    • Conclusions and future perspectives
    • References
  • 53. The epidemiology of EBV and its association with malignant disease
    Henrik Hjalgrim, Jeppe Friborg, and Mads Melbye.
    • EPSTEIN-BARR VIRUS EPIDEMIOLOGY
    • EBV viral load epidemiology
    • Infectious mononucleosis
    • Chronic active EBV infection
    • X-linked lymphoproliferative syndrome
    • Epstein–barr virus and malignant neoplasms
    • References
  • 54. The epidemiology of KSHV and its association with malignant disease
    Jeffrey N. Martin.
    • Introduction
    • Acknowledgments
    • References
  • 55. EBV-induced oncogenesis
    Nancy Raab-Traub.
    • Introduction
    • EBV infection in vivo
    • Characteristics of latent infection
    • Malignancies associated with EBV
    • Contributing factors
    • Summary and future considerations
    • References
  • 56. KSHV-induced oncogenesis
    Don Ganem.
    • Primary effusion lymphoma (PEL)
    • Multicentric Castleman’s disease (MCD)
    • Kaposi’s sarcoma
    • KSHV and KS: the big picture
    • KSHV gene expression in KS
    • Conclusions
    • References
• IV. Non-human primate herpesviruses
  Editors: Ann Arvin, Patrick S. Moore, and Richard Whitley.
  • 57. Monkey B virus
    Julia Hilliard.
    • Introduction
    • History
    • The virus
    • Pathology and pathogenesis
    • Latency
    • Epidemiology
    • Host immune responses
    • Clinical manifestations of disease
    • Diagnosis
    • Control of B virus infection
    • Conclusions
    • References
  • 58. Simian varicella virus
    Ravi Mahalingam and Donald H. Gilden.
    • Introduction
    • Similarities between SVV and VZV
    • Simian varicella virus genome
    • SVV pathogenesis
    • Acknowledgments
    • References
  • 59. Primate betaherpesviruses
    Peter A. Barry and W. L. William Chang.
    • Natural history
    • Infection in immunocompetent hosts
    • Infection in non-immunocompetent hosts
    • Summary
    • Acknowledgments
    • References
  • 60. Gammaherpesviruses of New World primates
    Bernhard Fleckenstein and Armin Ensser.
    • Introduction
    • Herpesvirus saimiri
    • Herpesvirus ateles
    • Lymphocryptoviruses of New World primates
    • Conclusions
    • Acknowledgments
    • References
  • 61. EBV and KSHV – related herpesviruses in non-human primates
    Damania Blossom.
    • Introduction
    • Nomenclature
    • Evolution of New and Old World lymphocryptoviruses
    • Lymphocryptoviruses of Old World monkeys
    • The rhesus LCV genome
    • Latency, immune-modulatory and transforming genes of rhesus LCV
    • Rhesus LCV as an animal model system for EBV
    • Other lymphocryptoviruses in Old World primates
    • Lymphocryptoviruses of New World monkeys
    • New World primates as an animal model system for EBV
    • Evolution of New and Old World rhadinoviruses
    • Rhadinoviruses of Old World primates
    • Retroperitoneal fibromatosis herpesviruses: RFHVMm and RFHVMn
    • Rhesus monkey rhadinovirus (RRV)
    • RRV as an animal model system for KSHV
    • Conclusions
    • Acknowledgments
    • References
• V. Subversion of adaptive immunity
  Editors: Richard Whitley and Ann Arvin.
  • 62. Herpesvirus evasion of T-cell immunity
    Benjamin E. Gewurz, Jatin M. Vyas, and Hidde L. Ploegh.
    • Disruption of class Ⅰ MHC antigen presentation
    • Disruption of class Ⅱ MHC antigen presentation
    • Conclusions
    • Acknowledgments
    • References
  • 63. Subversion of innate and adaptive immunity: immune evasion from antibody and complement
    Lauren M. Hook and Harvey M. Friedman.
    • Role of the herpesvirus IgG Fc receptor in immune evasion
    • Herpes simplex virus FcγR
    • Human CMV FcγR
    • Varicella zoster FcγR
    • vFcγRs on non-human mammalian herpesviruses
    • Summary of vFcγR studies
    • Role of the herpesvirus complement receptors in immune evasion
    • Strategies employed by human herpesviruses to evade complement immunity
    • Strategies employed by non-human mammalian herpesviruses to evade complement immunity
    • Summary of viral complement regulatory proteins
    • References
• VI. Antiviral therapy
  Editors: Ann Arvin and Richard Whitley.
  • 64. Antiviral therapy of HSV-1 and -2
    David W. Kimberlin and Richard J. Whitley.
    • Introduction
    • First-line antiviral agents for HSV-1 and HSV-2 infections
    • Famciclovir/penciclovir
    • Valaciclovir
    • Second-line antiviral agents for HSV-1 and HSV-2 infections cidofovir
    • Foscarnet
    • Ganciclovir
    • Valganciclovir
    • References
  • 65. Antiviral therapy of varicella-zoster virus infections
    John W. Gnann Jr.
    • Introduction
    • Diagnosis
    • Drugs with activity against VZV
    • Clinical indications for therapy
    • Clinical indications for prophylaxis
    • Drug-resistant varicella-zoster virus
    • References
  • 66. Antiviral therapy for human cytomegalovirus
    Paul D. Griffiths and Michael Boeckh.
    • Introduction
    • Licensed drugs and mechanism of action
    • Clinical efficacy; challenges for achieving clinical benefit
    • Laboratory diagnosis
    • Clinical indications for antiviral prophylaxis and dosage regimens
    • Conclusions
    • Resistance
    • Patterns of cross-resistance
    • References
  • 67. New approaches to antiviral drug discovery (genomics/proteomics)
    Mark N. Prichard.
    • Introduction
    • Development of bioinformatics and computational tools
    • Impact of genomics and related fields on herpesvirus research
    • New resources for use in drug discovery
    • Application of new technologies to cell-based antiviral assays
    • Application of new technologies to biochemical assays
    • Application of new technologies to functional assays
    • Application of new technologies to characterize mechanism of action and spectrum of activity
    • Conclusions
    • Acknowledgment
    • References
  • 68. Candidate anti-herpesviral drugs; mechanisms of action and resistance
    Karen K. Biron.
    • The drug development process: an overview
    • Host cell targets as an approach to virus inhibition
    • Antiviral targets in early replication events
    • Antiviral targets in the herpesvirus DNA replication complex
    • Inhibitors of DNA processing and packaging
    • Antivirals with activity against EBV, HHV-6, HHV-7, and HHV-8
    • Conclusions
    • References
• VII. Vaccines and immunotherapy
  Editors: Ann Arvin and Koichi Yamanishi.
  • 69. Herpes simplex vaccines
    George Kemble and Richard Spaete.
    • Introduction
    • History of HSV vaccine development
    • Development of live, attenuated vaccines
    • Subunit vaccines
    • Other approaches to vaccination
    • Conclusions
    • References
  • 70. Varicella-zoster vaccine
    Anne A. Gershon.
    • Varicella vaccines: background
    • History of development of the live attenuated vaccine
    • Virology of the attenuated Oka strain of VZV
    • Safety of the varicella vaccine for healthy individuals
    • Immunogenicity of varicella vaccine in healthy children and adolescents
    • Efficacy and post-licensure effectiveness of varicella vaccine
    • Considerations of vaccine use
    • Persistent questions regarding varicella vaccine
    • Does immunity to varicella wane with time after immunization?
    • Zoster: effects and potential effects on its incidence in the vaccine era
    • Vaccination to prevent zoster in the elderly
    • Use of inactivated varicella vaccine in patients at high risk to develop zoster
    • Recent developments
    • Conclusions
    • References
  • 71. Human cytomegalovirus vaccines
    Thomas C. Heineman.
    • Cytomegalovirus and human disease
    • The case for a cytomegalovirus vaccine
    • Natural immunity confers protection
    • Immunology of HCMV protection
    • Vaccine development
    • Challenges for HCMV vaccine development
    • Summary
    • References
  • 72. Epstein–barr virus vaccines
    Andrew J. Morgan and Rajiv Khanna.
    • Introduction
    • Vaccines to prevent infectious mononucleosis
    • Vaccines to prevent post-transplant lymphoproliferation disease
    • Therapeutic vaccines to prevent Hodgkin’s disease and nasopharygeal carcinoma
    • Therapeutic vaccines for Burkitt’s lymphoma
    • Conclusions
    • References
  • 73. DNA vaccines for human herpesviruses
    Thomas G. Evans and Mary Wloch.
    • General design of DNA vaccines
    • DNA vaccines for specific human herpesviruses cytomegalovirus
    • Herpes simplex virus 1 and 2
    • Varicella-zoster virus
    • Epstein–Barr virus
    • Summary
    • References
  • 74. Adoptive immunotherapy for herpesviruses
    Ann M. Leen, Uluhan Sili, Catherine M. Bollard, and Cliona M. Rooney.
    • Introduction
    • Therapy for herpesvirus-related infections and diseases
    • Cytomegalovirus
    • Epstein–Barr virus
    • T-cell activation
    • Strategies for producing T-cells for adoptive immunotherapy
    • Adoptive immunotherapy for cytomegalovirus
    • Adoptive immunotherapy for EBV post-transplant lymphoproliferation disease
    • Adoptive immunotherapy for EBV post-solid organ transplant
    • Adoptive transfer of EBV-specific CTL for Hodgkin’s lymphoma
    • Adoptive transfer of EBV-specific CTL for nasopharyngeal carcinoma
    • Multivirus-specific CTL lines
    • CMV and EBV immunotherapy in HIV positive individuals
    • Alternative approaches for activating virus-specific CTLs
    • Conclusions and future considerations
    • References
  • 75. Immunotherapy of HSV infections – antibody delivery
    David M. Kimberlin.
    • Immune responses following HSV infection
    • Human studies suggesting of protection by HSV antibodies
    • Animal models of antibody immunotherapy in HSV infection and disease
    • Limitations of antibody immunotherapy
    • Summary
    • References
• VIII. Herpesviruses as therapeutic agents
  Editors: Richard Whitley and Bernard Roizman.
  • 76. Herpesviruses as therapeutic agents
    Frank Tufaro and James M. Markert.
    • Introduction
    • Properties of therapeutic HSV vectors
    • Properties of non-replicating HSV vectors for therapeutic use
    • Use of HSV vectors to modify the nervous system
    • Towards optimizing HSV vectors for therapeutic use
    • Non-replicating vectors: current trends
    • Oncolytic HSV
    • Oncolytic HSV: current directions
    • References
• Plates

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