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Blood, Vol. 92 No. 5 (September 1), 1998:
pp. 1685-1696
Human Herpesvirus 7 Infection Induces Profound Cell Cycle
Perturbations Coupled to Disregulation of cdc2 and Cyclin B and
Polyploidization of CD4+ T Cells
Paola Secchiero,
Lucia Bertolaso,
Luca Casareto,
Davide Gibellini,
Marco Vitale,
Kristi Bemis,
Arrigo Aleotti,
Silvano Capitani,
Genoveffa Franchini,
Robert C. Gallo, and
Giorgio Zauli
From the Institute of Human Virology, University of Maryland at
Baltimore, Baltimore, MD; the Institute of Human Anatomy, University of
Ferrara, Ferrara, Italy; the Basic Research Laboratory, National Cancer
Institute, National Institutes of Health, Bethesda, MD; the Institute
of Microbiology, University of Bologna, Bologna, Italy; and the
Department of Biomedical Sciences and Biotechnology, Human Anatomy
Section, Brescia, Italy.
Human herpesvirus 7 (HHV-7) infection of both primary
CD4+ T lymphocytes and SupT1 lymphoblastoid T-cell line
induced a progressive accumulation of cells exibiting a gap 2/mitosis
(G2/M) and polyploid content coupled to an increased cell
size. The expression of both cyclin-dependent kinase cdc2 and cyclin B
was increased in HHV-7-infected cells with respect to the uninfected
ones. Moreover, the simultaneous flow cytometric analysis of cyclin B
and DNA content showed that cyclin B expression was not only increased
but also unscheduled with respect to its usual cell cycle pattern.
However, the levels of kinase activity associated to cdc2 were
decreased in HHV-7-infected cells with respect to
uninfected cultures. To elucidate the origin of the enlarged
HHV-7-infected cells, extensive electron and confocal microscopy
analyses were performed. Membrane fusion events associated to
cytoplasmic bridges, which characterize the formation of syncytia, were
never observed. On the other hand, analysis of serial sections of the
same cells strongly suggested that enlarged HHV-7-infected cells
contained a single polylobated nucleus. This was confirmed by flow
cytometry analysis performed on nuclei isolated from
HHV-7-infected cells, which showed multiple peaks with a DNA content
>4n. Taken together, these data indicate that giant cells, which
represent the hallmark of in vitro HHV-7 infection, arise from single
CD4+ T cells undergoing a process of polyploidization.
© 1998 by The American Society of Hematology.

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