Blood, Vol. 95 No. 2 (January 15), 2000:
pp. 487-493
In vitro infection of megakaryocytes and their precursors by
human cytomegalovirus
Kirsten Crapnell,
Esmail D. Zanjani,
Aniruddho Chaudhuri,
Joao L. Ascensao,
Stephen St. Jeor, and
Jaroslaw P. Maciejewski
From the Departments of Cellular and Molecular Biology, Internal
Medicine, and Microbiology, University of Nevada Medical School, Reno,
NV.
Apart from congenital human cytomegalovirus (HCMV) infection,
manifest HCMV disease occurs primarily in immunocompromised patients.
In allogeneic bone marrow transplantation, HCMV is frequently associated with graft failure and cytopenias involving all
hematopoietic lineages, but thrombocytopenia is the most commonly
reported hematologic complication. The authors hypothesized that
megakaryocytes (MK) may be a specific target for HCMV. Although the
susceptibility of immature hematopoietic progenitors cells to HCMV has
been established, a productive viral life cycle has only been linked to
myelomonocytic maturation. The authors investigated whether HCMV can
also infect MK and impair their function. They demonstrated that HCMV
did not affect the thrombopoietin (TPO)-driven proliferation of
CD34+ cells until MK maturation occurred. MK challenged
with HCMV showed a 50% more rapid loss of viability than mock-infected
cells. MK and their early precursors were clearly shown to be
susceptible to HCMV in vitro, as evidenced by the presence of HCMV in
magnetic column-purified CD42+ MK and 2-color fluorescent
staining with antibodies directed against CD42a and HCMV pp65 antigen.
These findings were confirmed by the infection of MK with a laboratory
strain of HCMV containing the 
-galactosidase (-gal) gene. Using
chromogenic -gal substrates, HCMV was detected during MK
differentiation of infected CD34+ cells and after
infection of fully differentiated MK. Production of infectious virus
was observed in cultures infected MK, suggesting that HCMV can complete
its life cycle. These results demonstrate that MK are susceptible to
HCMV infection and that direct infection of these cells in vivo may
contribute to the thrombocytopenia observed in patients infected with HCMV.
