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Parvovirus B19-induced perturbation of human megakaryocytopoiesis in vitro
A Srivastava, E Bruno, R Briddell, R Cooper, C Srivastava, K van Besien and R Hoffman
Department of Medicine, Walther Oncology Center, Indiana University School
of Medicine, Indianapolis 46202-5120.
Parvovirus B19 infection leads to transient aplastic crises in individuals
with chronic hemolytic anemias or immunodeficiency states. An additional
unexplained sequela of B19 infection is thrombocytopenia. Because B19 is
known to have a remarkable tropism for human erythropoietic elements, and
is not known to replicate in nonerythroid cells, the etiology of this
thrombocytopenia is uncertain. We sought to define the pathobiology of
B19-associated thrombocytopenia by examining the role of B19 on in vitro
megakaryocytopoiesis. B19 infection of normal human bone marrow cells
significantly suppressed megakaryocyte (MK) colony formation compared with
mock-infected cells. No such inhibition was observed with a nonpathogenic
human parvovirus, the adeno-associated virus 2 (AAV). The B19-MK cell
interaction was also studied at the molecular level. Whereas low-density
bone marrow cells containing erythroid precursor cells supported B19 DNA
replication, no viral DNA replication was observed in B19-infected
MK-enriched fractions as determined by the presence of viral DNA
replicative intermediates on Southern blots. However, analysis of total
cytoplasmic RNA isolated from B19-infected MK fractions showed a low-level
expression of the B19 genome as detected by quantitative RNA dot blots as
well as by Northern analysis. Furthermore, a frame-shift mutation in a
recombinant AAV-B19 hybrid genome segment that encodes the viral
nonstructural (NS1) protein significantly reduced the observed inhibition
of MK colony formation. These studies indicate tissue- tropism of B19
beyond the erythroid progenitor cell, and lend support to the hypothesis
that B19 genome expression may be toxic to cell populations that are
nonpermissive for viral DNA replication.
Volume 76,
Issue 10,
pp. 1997-2004,
11/15/1990
Copyright © 1990 by The American Society of Hematology
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