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Blood, Vol. 96 No. 1 (July 1), 2000:
pp. 126-131
Infection of CD34+ hematopoietic progenitor cells
by human herpesvirus 7 (HHV-7)
Prisco Mirandola,
Paola Secchiero,
Sabina Pierpaoli,
Giuseppe Visani,
Loris Zamai,
Marco Vitale,
Silvano Capitani, and
Giorgio Zauli
From the Institute of Normal Morphology, G. D'Annunzio University
of Chieti, Chieti, Italy; Department of Morphology and Embryology,
Human Anatomy Section, University of Ferrara, Ferrara, Italy; Institute
of Hematology, University of Bologna, Bologna, Italy; Institute of
Morphological Sciences, University of Urbino, Campus Scientifico Loc
Urbino, Italy; and Department of Biomedical Sciences and Biotechnology,
Human Anatomy Section, University of Brescia, Brescia, Italy.
To investigate the tropism of the T-lymphotropic human
herpesvirus 7 (HHV-7) for hematopoietic progenitors, cord blood
CD34+ cells were inoculated in vitro with HHV-7 and then
induced to differentiate along the granulocytic and erythroid lineages
by the addition of appropriate cytokine cocktails. In semisolid assays, HHV-7 modestly affected the growth of committed
(granulocytic/macrophagic and erythroid) progenitors, whereas it
significantly decreased the number of pluripotent
(granulocytic/erythroid/ monocytic/megakaryocytic) progenitors. Such
inhibitory effect was completely abrogated by incubating HHV-7 inoculum
with anti-HHV-7 neutralizing serum. In liquid cultures, HHV-7 hastened
maturation along the myeloid but not the erythroid lineage, as
demonstrated by the up-regulation of CD33 early myeloid antigen at day
7 of culture, and of CD15 and CD14 antigens at day 15. Moreover, HHV-7
messenger RNA was detected by reverse transcriptase-polymerase chain
reaction (RT-PCR) in cells maturating along both the myeloid and the
erythroid lineages. To evaluate the relevance of these in vitro
findings, the presence of HHV-7 was investigated in bone marrow (BM)
unfractionated mononuclear cells (MCs) as well as in purified
CD34+ and CD34 cell subsets, obtained from
14 normal adult donors. HHV-7 DNA was detected by DNA-PCR in 4 of 7 BMMC samples, and it was found to be associated with both the
CD34 (2 of 7) and the CD34+ (1 of 7)
fractions. These data indicate that HHV-7 infects BM cells in vivo and
shows the ability to affect the survival/differentiation of
CD34+ hematopoietic progenitors in vitro by inhibiting
more ancestral progenitors and perturbing the maturation of myeloid cells.
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