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Plate 1 Peripheral blood mononuclear cells (PHA stimulated), cultured from AIDS patient with B-cell lymphoma, showing large refractile cells. (see page 4).
Plate 2 Giemsa-stained peripheral blood mononuclear cells, containing refractile cells, showing multinucleated giant cells. (see page 4).
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Plate 3 Immunofluorescent staining of HHV-6-infected human cordblood mononuclear cells with patient GS serum. (see page 6).
Plate 4 Sub-families of Human Herpesviruses. (see page 8).
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Plate 5 CryoEM imaging and 3D reconstruction HSV-6 capsid. (a) A gallery of cryoEM particle images of HHV-6 capsids. (b) Shaded surface representation of HHV-6 capsid reconstruction at 30 A˚ resolution. The structure is color coded according to capsid radius so that the capsid shell is in yellow, the triplexes are in green, and the upper domains of the pentons and hexons are in purple. (see page 17).
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Plate 6 Comparison of HSV-1, HCMV, and KSHV capsids. A penton and a hexon are extracted from the cryoEM structures for detail comparison. Overall structure is similar; minor differences in hexon morphology may be a result of different structures of the distally located SCPs. (Modified from a figure by P. Lo). (see page 18).
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Plate 7 Indirect immunofluorescence assay of HHV-6-infected cells. The HSB-2 cells infected with HHV-6A (strain GS) were stained with monoclonal antibody for IE1 (a) U27 (b) or gB (c) at 86 h p.i. (a) IE1 locates in nucleus with punctuated pattern. (b) U27 locates in nucleus like forming replication compartment. (c) gB locates in the cytoplasm. (see page 49).
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Plate 8 Cellular reactions in HHV-6-infected cells. Top Row: HHV-6A-infected HSB2 cells in culture: blastic transformation of infected cells (left) and nuclear inclusions in semithin section (right). Center Row: Prominent giant cell formation after infection with HHV-6A: SupT1 cells in culture (left) and L428 Hodgkin cell line (semithin section of culture; right). Bottom Row: Antigen expression in HHV-6Ainfected SupT1 cells: p41 early antigen (left) and HAR3 (i.e. mixture of late gp antigens; right). All APAAP immunohistochemistry. (see page 136).
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Plate 9 Some characteristic tissue reactions in HHV-6 infections. Top Row: Blastic transformation of cells in tonsils with prominent nucleoli (left) with expression of HHV-6 p41 early antigen (red cells in APAAP reaction; right). Upper Center Row: Prominent apoptosis of HHV-6 infected cells in Kikuchi’s lymphadenitis (left); hematopoietic stem cells in bone marrow expressing HHV-6 p41 antigen (red dots in APAAP reaction; right). Lower Center Row: Expression of HHV-6 gp135 in epithelial cells of the salivary gland (lip biopsy; left); HHV-6A-associated lymphoid interstitial pneumonitis, LIP, in an HIV infected patient (red cells carry p41 HHV-6 antigen; APAAP reaction). Bottom Row: Acute necrotizing encephalitis with HHV-6 p41 and DNA expression in numerous astroglial cells (red cells by APAAP left, black dots for HHV-6 DNA by in situ hybridization (right; Wagner et al., 1997). (see page 140).
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Plate 10 Facial edema and an exfoliative dermatitis in DRESS. (see page 152).
Plate 11 Typical skin eruption observed in patient with primary HHV-6 infection. Maculopapular skin rash is observed on the trunk and extremity. (see page 164).
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P U
F T
T
Plate 12 Enanthema with Nagayama’s papules at the parauvular region (P) and fossa supratonsillaris (F), (U) Uvula, (T) tonsils; on the right a scheme of the throat with the photo section. Tonsillar hyperplasia in primary HHV-6 infection (lower photo with courtesy of G. Bertram, University ENT Clinic Cologne, Germany). (see page 177).
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Plate 13 Top row: non-specific interstitial pneumonitis (NIP) in patient with acute necrotizing encephalitis following primary HHV-6 infection (Wagner et al., 1997). Bottom row: lymphoid interstitial pneumonitis (LIP) in patient with HIV infection and HHV-6 reactivation red cells immunohistochemical APAAP reaction for HHV-6 p41 antigen (courtesy of G. Krueger, Immunopathology Laboratory, University of Cologne, Germany). (see page 180).
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Plate 14 Expression of DR7 protein in tissue samples from patients suffering from HD, previously detected positive by HHV-6 structural monoclonal antibodies. DR7 was strongly positive and was principally found in RS cells, and to a lesser extent in other lymphoid cells. (see page 196).
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Plate 15 (A) Postmortem specimen showing a dilatation of the left ventricular cavity and thinning of the left ventricle and intraventricular septum; (B) A loss of myofibers with interstitial fibrosis (HE stain, 40); and (C) Inflammatory cellular infiltration (mainly rounded cell) (HE stain, 1 0 0) was observed in the left ventricle. (see page 229).
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Plate 16 HHV-6 infection of vascular endothelial cells. Top: Splenic sinusoidal endothelial cells containing HHV-6 late antigens (red-stained cells; APAAP reaction using HAR 1-3 antibody). Bottom: HHV-6 DNA in endothelial cells of cardiac arteriole in an AIDS patient (left) and of a brain venule (right) in a case of necrotizing encephalitis in a child with active HHV-6 infection (black cells; in situ hybridization with pZVH14 probe). (see page 235).
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Plate 17 Various forms of myocarditis accompanying HHV-6 reactivation in AIDS patients (hematoxylin and eosin stain of autopsy specimens). Lower right shows an interstitial cardiac arteriole from such cases containing HHV-6 DNA (in situ hybridization with pZVH14 probe). (see page 237).
Plate 18 Axial SPECT image showing multiple foci of decreased perfusion (arrows) in the brain. (see page 257).
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Plate 19 Neuropathology of acute C. jacchus EAE. Perivascular inflammatory demyelinating infiltrates in spinal cord and brain periventricular white matter (left, middle). High-power view to show monocyte/ macrophage infiltration (LFB/PAS). (see page 310).
(A)
(B)
(C)
Plate 20 A, Coronal MRI section showing T2 hyper-intensity lateral to median CSF space in pons (arrow). B, Corresponding demyelinating inflammatory infiltrate (animal 190-94; LFB/PAS, also see Fig. 1). C, Staining for early nuclear antigen p41/p38 (Advanced Biotechnologies, Inc.), demonstrating viral persistence/replication within lesions. Positively stained cells (arrows) have not yet been formally identified but appear to be oligodendrocytes. (see page 313).