Cover -- Contents -- Foreword by Robert Gallo -- Foreword by Ronald Glaser and Marshall Williams -- Preface -- Part I: General Virology -- Discovery and Classification of Human Herpesvirus-6 (HHV-6) -- Discovery -- Nomenclature and classification -- References -- Ultrastructure and Assembly of Human Herpesvirus-6 (HHV-6) -- Introduction -- Herpesvirus-6 assembly and maturation -- Three-dimensional structure of HHV-6 capsid -- Comparision of the HHV-6 cappsid structure with those of other human herpesviruses -- Conclusion -- References -- HHV-6 Genome: Similar and Different -- Genome classification and biology -- Genomes, cellular tropism and laboratory culture -- Genome structure and repetitive sequence -- Genome rearrangements and relationship to other herpesviruses -- Genome composition and general molecular biology -- Herpesvirus conserved and HHV-6-specific genes -- Genomes and HHV-6 strains -- Acknowledgements -- References -- Proteins of HHV-6 -- Introduction -- IE proteins -- U16/U17 -- U53, proteinase -- U69, kinase -- Cellular homologues -- U94, AAV-2 rep homologue -- Envelope glycoproteins -- U39, gB -- U48 and U82, gH and gL -- U100, gQ -- U47, gO -- U11 -- U14 -- U27 -- Perspective -- References -- Biological Features of HHV-6 -- Introduction -- HHV-6 cellular receptor -- Species specificity -- Cellular tropism of HHV-6 -- Target cells in vitro -- Cellular and tissue host range in vivo -- Biological effects of HHV-6 on the host cell -- Cytopathic effects -- Latent infection -- Cellular transformation -- Immune modulation -- Human lymphoid tissue ex vivo: a new model for the study of HHV-6 pathogenesis -- Dysregulation of complement activation -- References -- Part II: Diagnosis and Epidemiology -- Strain Variants of HHV-6 -- Introduction -- Epidemiology -- Molecular biology -- Biological aspects of variants A and B.

Reactivity of monoclonal antibodies to HHV-6 variants A and B -- Disease associations of HHV-6A and -6B variants -- Roseola infantum -- CNS disease -- Epilepsy and HHV-6B -- Transplantation and HHV-6 variants -- HHV-6 (variants A and B) and multiple sclerosis -- HHV-6A and chronic fatigue syndrome (CFS) -- Concluding remarks -- References -- Serologic Testing for Acute and Chronic Infection -- Introduction -- Serologic assays -- Techniques -- Immunofluorescence assays -- Enzyme immunoassays -- Neutralization assays -- HHV-6 antigens involved in serologic testing -- Characterization of HHV-6-specific antibodies -- Serologic findings -- Seroprevalence studies -- Primary infection -- Latent infection and reactivations -- Central nervous system diseases -- Pending questions and perspectives -- Acknowledgments -- References -- Molecular Testing for HHV-6 Infection -- Introduction -- Primary infection: characteristics and diagnostic considerations -- PCR analysis of cell-free body fluids -- Reverse transcription PCR analysis -- Quantitative PCR analysis of HHV-6 DNA in PBMC or blood -- Detection of virus variants -- Other assay approaches -- Future assay methods -- PCR-based assays: general considerations and molecular underpinnings -- Commercially available tests -- General considerations for current molecular assays -- References -- Epidemiology of HHV6 -- The epidemiology of roseola from historical observations -- Seroepidemiologic studies of HHV6 infection -- Acquisition of HHV6 infection during childhood -- Acquisition of HHV6 infection according to variant -- Factors affecting acquisition of HHV6 infection -- Mode of transmission -- Postnatal infection -- Congenital infection -- Incubation period -- Summary -- References -- Part III: Clinical Pathology -- Pathologic Features of HHV-6 Disease -- Introduction.

Cell and tissue tropism and strain differences -- General cellular pathology of HHV-6 infection -- Primary infection -- Reactivation and endogenous reinfection -- Lymphatic and hematopoietic system (see also chapters 14 and 15) -- Central nervous system (see also chapter 16) -- Cardiovascular system (see also chapter 17) -- Other organs and tissues (see also chapters 13 and 18) -- Conclusions -- References -- Systemic Reactions to HHV-6 Infection -- Introduction -- From the anticonvulsant hypersensitivity syndrome to the DRESS -- Clinical spectrum and systemic manifestations -- DRESS and HHV-6: the first reports -- HHV-6 reactivation in DRESS: ''innocent bystander'' or causal agent of systemic symptoms -- HHV-6: a helper virus for other herpesviruses in DRESS? -- Pathophysiology of HHV-6 reactivation in DRESS -- Therapeutic implications -- Conclusion -- References -- HHV-6 and the Integument -- Introduction -- Exanthem subitum -- Skin rash and HHV-6 reactivation in hematopoietic stem cell transplant recipient -- Drug-induced hypersensitivity syndrome and HHV-6 -- Pityriasis rosea and HHV-6 -- Pathogenesis of skin manifestations due to HHV-6 infection -- References -- HHV-6 and the Respiratory System -- Introduction -- Primary HHV-6 infection and the respiratory tract -- Clinical features of primary HHV-6 infection in children -- Pharynx, tonsils, eyes and ears -- Upper respiratory tract -- Lower respiratory tract -- Non-primary HHV-6 infection and the respiratory tract -- Interstitial pneumonia in not overtly immunocompromised persons -- Pneumonitis in immunosuppressed patients -- Resume -- Acknowledgment -- References -- HHV-6 and the Lympho-Hematopoietic System -- Introduction -- In vitro data -- Evolution of techniques used and evolution of findings -- HHV-6 infection can induce atypical lymphoproliferations.

The main LD associated with HHV-6, in immunocompetent subjects, is probably HD -- Characteristics of HHV-6 found in lymph nodes -- Viral quantification -- HHV-6B is more often detected than HHV-6A -- HHV-6 is found essentially in scleronodular HD in young adults -- HHV-6 may be associated with EBV -- HHV-6 is present in different cell types and also in RS cells -- HHV-6 can also be detected in other lymphoproliferative diseases -- NHL in immunocompetent subjects -- B-cell lymphomas -- T-cell lymphomas -- Cerebral lymphomas and lymphomas with a predilection for the nervous system -- Lymphomas in SS patients -- HHV-6-associated lymphomas in immunocompromised individuals -- Post-transplant LD -- AIDS-related LD -- Acute lymphoblastic leukaemia -- Different mechanisms have been proposed for HHV-6 in lymphoproliferative diseases -- HHV-6 exhibits transforming capacities -- HHV-6 retains p53 within the cytoplasm -- HHV-6 can transactivate genes -- Transactivation of human genes -- Transactivation of viral genes -- EBV transactivation -- HHV-8 transactivation -- HHV-6 has the ability to integrate into host cell chromosomal DNA -- HHV-6 may exert a role in cell proliferation by dysregulation of cytokine network -- Conclusion -- References -- Human Herpesvirus-6 and the Cellular Immune System -- Introduction -- Isolation history: association with immunodeficiency disorders -- Subversion of the immune system -- In -- vitro studies: Th1 to Th2 switch -- Reactivation: transplantation -- Solid organ transplant -- Bone marrow transplant -- Current immunological tools -- Disease associations between HHV-6 infection and multiple sclerosis, fibromyalgia, and chronic fatigue syndrome -- Method: rapid immune function assay -- Results: comparing healthy adults, stable transplant patients, HIV-infected patients, and CFS patients -- Discussion and conclusions.

References -- HHV-6 and the Central Nervous System -- HHV-6 infection of the central nervous system -- HHV-6 in seizure disorders -- The association of HHV-6 with MS -- HHV-6 and PML -- Acknowledgments -- References -- HHV-6 and the Cardiovascular System -- Introduction -- Case report -- Discussion -- References -- HHV-6 in Cardiovascular Pathology -- Introduction -- Diseases of blood vessels -- Diseases of the heart -- Conclusions -- References -- HHV-6, the Liver and the Gastrointestinal Tract -- Introduction -- HHV-6 and hepatitis -- HHV-6 association with other liver disease -- Pathogenesis of HHV-6-associated hepatitis -- HHV-6 and gastrointestinal tract -- References -- HHV-6 in Chronic Fatigue Syndrome -- Chronic fatigue syndrome -- Immune dysfunction -- Viral implication -- Proposed pathogenic model of CFS -- Identifying subsets among the CFS population -- HHV-6 association with CFS -- HHV-6 in CNS of CFS patients -- HHV-6 therapy in CFS patients -- Immunomodulatory therapy for HHV-6 in CFS patients -- HHV-6 diagnostic testing in CFS patients -- Future research -- Summary -- References -- HHV-6 and HIV-1 Infection -- Introduction -- In vitro interactions between HHV-6 and HIV-1 -- Productive coinfection of CD4+ T cells by HHV-6 and HIV-1 -- HIV-1 LTR transactivation by HHV-6 -- Effects of HIV-1 on HHV-6 replication -- Direct virion- virion interactions -- De nova induction of CD4 expression -- Induction of inflammatory cytokines that modulate HIV replication -- Mechanisms of direct immunological damage by HHV-6 -- In vivo studies of HHV-6 infection in HIV-1 disease -- HHV-6 as an opportunistic agent in AIDS -- Correlation between HHV-6 replication and HIV-1 disease progression -- Experimental coinfection models ex vivo and in vivo.

Coinfection studies in structurally intact human lymphoid tissue ex vivo: does HHV-6 favor the phenotypic switch of HIV-1?.