Anmerkung: Front Cover -- Human Herpesviruses HHV-6A, HHV-6B, and HHV-7 -- Copyright Page -- Contents -- List of Contributors -- Foreword by Philip E. Pellett -- Foreword by Yoshizo Asano -- Dedication -- 1 HHV-6A and HHV-6B Officially Classified as Distinct Viruses -- Introduction and Classification History -- Distinct Epidemiology and Disease Associations -- Acknowledgment -- References -- 2 Practical Diagnostic Procedures for HHV-6A, HHV-6B, and HHV-7 -- An Overview of Diagnostic Strategies -- Objectives -- Direct and Indirect Approaches -- Specimens -- Methods of Direct Diagnosis -- Cell Culture -- Antigen Detection -- Nucleic Acid Detection, Quantitation, and Sequencing -- Detection of DNA by in situ Hybridization -- Detection and Quantitation of DNA by PCR and Real-Time PCR -- Detection and Quantitation of Transcripts by RT-PCR -- Nucleotide Sequencing -- Differential Diagnosis of HHV-6A and HHV-6B Infection -- Antiviral Susceptibility Assays -- Serologic Methods -- Techniques -- Viral Antigens Used for Serologic Testing -- Characterization of Specific Antibodies -- Indications and Findings -- Primary Infection -- Chronic Infection and Reactivations -- Chromosomal Integration -- Epidemiology -- Therapeutic Follow-Up -- Conclusions: Practical Management of Diagnosis -- References -- 3 Pathologic Features of HHV-6A, HHV-6B, and HHV-7 Infection (Light and Electron Microscopy) -- Introduction -- Viral Infection and Pathogenesis -- Morphogenesis of Cell and Tissue Lesions -- Anatomic (Systemic) Pathology of Tissues and Organs -- Diagnostic Criteria -- Pathologic Lesions in Primary Infection -- Viral Persistence and Chromosomal Integration -- Pathologic Lesions in Reactivation and Endogenous Reinfection -- Morphology of Organ Systems in Reactivated Infections -- Cardiovascular System -- Respiratory System -- Gastrointestinal System. , Liver, Biliary System, and Pancreas -- Hematopoietic and Lymphatic System -- Endocrine System -- Urogenital System -- Skin and Soft Tissues -- Central Nervous System -- Autoimmune Disorders -- Virus Interactions -- References -- 4 HHV-6A, HHV-6B, and HHV-7 in Febrile Seizures and Status Epilepticus -- Introduction -- History of HHV-6, Roseola Infantum, and Febrile Seizures -- HHV-6B and Febrile Seizures -- HHV-6B and Recurrence of Febrile Seizures -- HHV-6A, HHV-6B, and HHV-7 in Children with Febrile Status Epilepticus -- HHV-6 and HHV-7 and Temporal Lobe Epilepsy -- HHV-6 Encephalitis in Immunocompetent Patients -- HHV-6 and Limbic Encephalitis in Immunosuppressed Patients -- Conclusions -- References -- 5 HHV-6A, HHV-6B, and HHV-7 in Encephalitis -- Introduction -- General Aspects and Neurotropism of Human Herpesvirus 6A Infection -- General Aspects of Human Herpesvirus 6B Infection -- Importance of Chromosomally Integrated HHV-6 in Neurological Conditions -- Human Herpesvirus 7 -- Clinical Presentation of HHV-6- or HHV-7-Associated Encephalitis -- Encephalitis Following a Primary HHV-6 or HHV-7 Infection in Immunocompetent Individuals -- Encephalitis Following Reactivation of HHV-6 or HHV-7 in Immunocompromised Patients -- Pathology and Pathogenesis -- Risk Factors -- Diagnosis -- Clinical Manifestations and Other Relevant Information -- General Laboratory Procedures -- Electroencephalography, Neuroimaging, and Histopathology -- Virological and Microbiological Investigations -- Differential Diagnosis -- Prognosis, Therapy, and Prevention -- Conclusions -- Acknowledgments -- References -- 6 Cognitive Dysfunction from HHV-6A and HHV-B -- Introduction -- The Difficulty of Attributing a Causal Role to HHV-6 in Encephalitis -- The Definition of Encephalitis -- Attributing Pathogenicity to What Is Typically a Ubiquitous Commensal. , Understandable Deficiencies in the Literature -- Inherited, Chromosomally Integrated Virus -- HHV-6 Encephalitis at the Time of Primary Infection -- Case Reports -- Case Series and Large Systematic Surveys -- HHV-6 Encephalitis in Immunocompetent Adults -- Case Reports -- Case Series and Large Systematic Surveys -- HHV-6 Encephalitis in Inherited, Chromosomally Integrated Virus -- HHV-6 Encephalitis in Hematopoietic Cell Transplantation Recipients -- Epidemiology of HHV-6 Encephalitis in the HCT Recipient -- Clinical Presentation of HHV-6 Encephalitis in HCT Recipients -- Laboratory Diagnosis in Encephalitis -- Inherited Chromosomally Integrated HHV-6 -- Treatment of Encephalitis -- Outcomes in Encephalitis -- Chronic Fatigue Syndrome -- Conclusion -- Acknowledgments -- References -- 7 HHV-6 and Multiple Sclerosis -- Introduction -- Multiple Sclerosis -- Genetic Factors in MS -- Geographical Distribution in MS -- Immigration Studies in MS -- Environmental Factors and MS -- Viruses and Multiple Sclerosis -- EBV and MS -- The Hygiene Hypothesis -- Animal Models of Virally Induced Demyelination -- Virally Induced Demyelination in Humans -- Oligoclonal Bands and IgG Index in MS -- Viruses Leading to MS Exacerbation -- Antiviral Effects of Interferon-β and MS -- HHV-6 and MS -- History of HHV-6 Link with MS -- Tissue Evidence of HHV-6 in MS -- DNA Evidence for HHV-6 in MS Outside of the CNS -- DNA Evidence for HHV-6 in MS in CSF -- Serological Evidence for HHV-6 in MS -- Effects of IFN-β on HHV-6 in MS -- Evidence for HHV-6A in MS -- Potential Mechanisms for HHV-6 Induced Autoimmunity in Ms -- Molecular Mimicry -- Bystander Activation -- Epitope Spreading -- Additional Mechanisms by Which HHV-6 May Affect Ms -- HHV-6 Leading to Apoptosis -- HHV-6 Causing Inflammation -- HHV-6 May Impair Remyelination -- HHV-6 and Glutamate Dysregulation. , HHV-6 and Impaired Phosphorylation of MBP -- HHV-6 and HERVs -- Conclusion -- References -- 8 Human Herpes Virus 6B in Mesial Temporal Lobe Epilepsy -- introduction -- Immunohistochemical and PCR Studies on Epilepsy Biopsy Samples -- Discussion -- References -- 9 HHV-6B and HHV-7 in Exanthema Subitum and Related Skin Diseases -- Introduction -- Exanthem Subitum and HHV-6B -- Exanthem Subitum and HHV-7 -- HHV-6B Reactivation in Severe Forms of Drug Allergy -- Acute Graft-Versus-Host Disease and HHV-6B -- Pathogenesis of Skin Manifestations Due to HHV-6B Infection -- References -- 10 HHV-6A and HHV-6B in Autoimmune Disease -- Introduction -- HHV-6 and Multiple Sclerosis -- Pathogenic Hypotheses for HHV-6-Induced Multiple Sclerosis -- HHV-6 and Autoimmune Connective Tissue Diseases -- Pathogenic Hypotheses for HHV-6-Induced Autoimmune Connective Tissue Diseases -- HHV-6 in Hashimoto's Thyroiditis -- Pathogenic Hypotheses for HHV-6-Induced Hashimoto's Thyroiditis -- References -- 11 HHV-6A and HHV-6B in Drug-Induced Hypersensitivity Syndrome/Drug Reaction with Eosinophilia and Systemic Symptoms -- Introduction -- DIHS/DRESS Defined -- Epidemiology -- DIHS/DRESS Pathophysiology -- Clinical Features and Laboratory Findings -- Initial Findings -- Flare-Ups and the Development of New Symptoms -- Histopathology -- Skin -- Lymph Nodes -- Liver -- Viral Reactivation -- HHV-6 -- Other Herpesviruses -- Visceral Involvements and Sequelae of DIHS/DRESS -- Visceral Involvement During the Course of DIHS/DRESS -- Hepatobiliary System -- Renal System -- Respiratory System -- Cardiovascular System -- Central Nervous System -- Gastrointestinal System -- Pancreatic System -- Other Organs -- Sequelae of DIHS/DRESS -- Differential Diagnosis -- Management and Treatment -- Conclusion -- Acknowledgment -- References -- 12 HHV-6A and HHV-6B in Solid Organ Transplantation. , Introduction -- HHV-6 Infections in Solid Organ Transplantation -- Epidemiology -- Clinical Perspectives -- Clinical Syndromes -- Indirect Sequelae -- Chromosomally Integrated HHV-6 (ciHHV-6) in Organ Transplant Patients -- Diagnosis of HHV-6 Infection -- Antiviral Treatment -- Concluding Remarks -- References -- 13 HHV-6A and HHV-6B in Recipients of Hematopoietic Cell Transplantation -- Introduction -- Epidemiology -- HHV-6 Reactivation -- Disease Associations -- Encephalitis -- Bone Marrow Suppression -- Other Disease Associations -- Pathogenesis -- Encephalitis -- Differential Diagnosis -- Diagnosis -- Chromosomal Integration -- Approach to Diagnosis -- Treatment -- Prevention -- Outcomes -- Conclusion -- References -- 14 The Immune Response to HHV-6 -- Introduction -- HHV-6 and Innate Immune Responses -- Toll-Like Receptors and Type I Interferon Responses -- NK Cell Responses -- Modulation of the Chemokine Network by HHV-6 -- Adaptive Immune Response to HHV-6 -- Antibody Response to HHV-6 -- Modulation of T-Cell Responses -- Direct Modulation in Infected Cells -- Indirect Modulation in Noninfected Cells -- T-Cell Responses to HHV-6 -- T-Cell Response to HHV-6 in Children -- T-Cell Response to HHV-6 in Transplant Recipients -- T-Cell Responses in Patients with Multiple Sclerosis -- T-Cell Responses to HHV-6 in Healthy Adults -- Antigen Specificity of the T-Cell Response to HHV-6 -- Functional Characterization of CD4+ T-Cell Responses to HHV-6 -- Cross-Reactivity Between HHV-6A and HHV-6B Epitopes -- Detection of HHV-6 Peptide-Specific CD4+ T-Cell Responses Ex Vivo Directly in PBMC -- Characterization of CD8+ T-Cell Responses -- Conclusions -- Acknowledgments -- References -- 15 Chromosomally Integrated HHV-6 -- Historical Perspectives on ciHHV-6 -- ciHHV-6 and Diagnosis of HHV-6 Active Infection. , Potential Clinical Outcomes Associated with ciHHV-6.