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Direct infection of CD34+ progenitor cells by human cytomegalovirus:
evidence for inhibition of hematopoiesis and viral replication
M Movassagh, J Gozlan, B Senechal, C Baillou, JC Petit and FM Lemoine
Laboratory for Biology and Therapy of Immune Pathology, Hospital Pitie
Salpetriere, Paris, France.
We successfully infected fluorescence-activated cell-sorted CD34+ cells
from normal cord blood by the human cytomegalovirus (HCMV) laboratory
strain Towne. An inhibitory effect of HCMV on clonogenic myeloid
progenitors was observed in primary methylcellulose cultures. After an
initial 7-day liquid culture of CD34(+)-infected cells, this inhibition was
further amplified in secondary methylcellulose cultures, then involving
both the myeloid and erythroid lineages. Under these conditions, viral DNA
was detected both in erythroid and myeloid colonies using the polymerase
chain reaction (PCR), but reverse transcription PCR (RT-PCR) failed to
detect viral RNA. In contrast, when CD34(+)-infected cells were maintained
in liquid suspension, both immediate, early, and late transcripts were
detected as soon as day 3. In addition, viral production was demonstrated
in the culture supernatants, thus confirming that a complete viral cycle
occurred under liquid conditions. Furthermore, by resorting cells into
CD34+ and CD34- fractions, we showed by RT-PCR that viral replication took
place in cells still expressing CD34 antigen, whereas no RNA was found in
more differentiated cells that had subsequently lost their CD34 antigen.
These findings suggest that HCMV replication can occur at the early steps
of progenitor differentiation and may be involved in the viral-induced
myelosuppression.
Volume 88,
Issue 4,
pp. 1277-1283,
08/15/1996
Copyright © 1996 by The American Society of Hematology

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