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Constitutive activation of U937 promonocytic cell clones selected for their
resistance to parvovirus H-1 infection
JA Lopez-Guerrero, B Rayet, M Tuynder, J Rommelaere and C Dinsart
Deutsches Krebsforschungszentrum, Applied Tumor Virology, Heidelberg,
Germany.
The human promonocytic cell line U937 is highly sensitive to the lytic
effect of the autonomous parvovirus H-1. Rare cell variants that resisted
H-1 virus infection could be isolated, of which four (RU1, RU2, RU3, and
RU4) were further characterized. In contrast to parental cells, the RU
clones sustained an abortive H-1 virus infection. Three of the clones
showed a significant decrease in the accumulation levels of the c-Myc
oncoprotein and in their capacity for forming tumors in immunodeficient
mice. Surprisingly, all RU clones resisted the suppressing effect of
12-O-tetradecanoylphorbol-13-acetate (TPA) on c- myc oncogene expression
and cell proliferation. In contrast, RU clones exhibited the TPA-induced
changes in membrane surface antigens and nonspecific esterase activities
that are characteristic of monocytic differentiation. Studies of the
activation steady-state of RU cells demonstrated the constitutive
production of significant amounts of nitric oxide (NO) and superoxide anion
(O-.2). Inhibitors of NO and O- .2, production sensitized all RU cells to
the killing effect of parvovirus H-1 and increased the production of
infectious viral particles. These data argue for the participation of
active oxygen species in macrophage defence mechanisms against parvovirus
infection. Moreover, the use of parvovirus H-1 as a selective agent in a
cell- colony formation assay allowed us to show that expression of defined
markers of monocytic differentiation can be uncoupled from suppression of
proliferation.
Volume 89,
Issue 5,
pp. 1642-1653,
03/01/1997
Copyright © 1997 by The American Society of Hematology
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