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Morphology, immunophenotype, and distribution of latently and/or
productively Epstein-Barr virus-infected cells in acute infectious
mononucleosis: implications for the interindividual infection route of
Epstein-Barr virus
I Anagnostopoulos, M Hummel, C Kreschel and H Stein
Institute of Pathology, Klinikum Benjamin Franklin, Free University Berlin,
Germany.
The present study was undertaken to unequivocally demonstrate the
morphology, immunophenotype, and localization of Epstein Barr virus
(EBV)-infected cells as well as the type of infection (latent versus
productive) in tonsils of acute infectious mononucleosis. Paraffin sections
from nine cases with clinical, serologic, and morphologic evidence of EBV
infection were analyzed for the detection of small transcripts, designated
EBER1 & 2, and BHLF1 by in situ hybridization (ISH) using
nonisotopically labeled probes. ISH was combined with immunohistology,
employing a broad panel of antibodies against B-, T-, epithelial-,
macrophage-, and follicular dendritic cell (FDC)-antigens. All
EBER-positive cells could be identified as lymphocytes, as they did not
exhibit any morphologic or immunologic characteristics of epithelial cells,
macrophages, or FDCs. A preferential accumulation of EBER-positive cells
was noted around crypts, within surface squamous epithelium, and in the
surroundings of necrosis. The majority of these lymphocytes could be shown
to be B cells, which morphologically included Reed-Sternberg (RS)-like
cells, immunoblasts, medium-sized lymphoid cells, as well as cells with
plasmacytoid differentiation. In all cases, a varying number of
EBER-positive T cells could be identified. ISH for BHLF1-RNA detection
showed that almost all cases contained single positive small lymphoid
cells, indicating a transition from latent to productive infection cycle.
Such cells could also be detected within the crypt epithelium reaching up
to its surface. Additional screening of 123 oropharyngeal mucosa samples
from patients without evidence of acute EBV-infection, using the polymerase
chain reaction for EBV-DNA detection combined with EBER- and BHLF1-ISH
showed single latently infected lymphocytes in only one case. Our data
imply that infected lymphocytes and not epithelial cells are, in fact, the
reservoir for EBV infection, and that these are the cells that participate
in the interindividual virus transfer.
Volume 85,
Issue 3,
pp. 744-750,
02/01/1995
Copyright © 1995 by The American Society of Hematology
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