Constitutive activation of U937 promonocytic cell clones selected for their resistance to parvovirus H-1 infection.
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.
López-Guerrero
J A
JA
Deutsches Krebsforschungszentrum, Applied Tumor Virology, Heidelberg, Germany.
Rayet
B
B
Tuynder
M
M
Rommelaere
J
J
Dinsart
C
C
D000818:Animals; D002454:Cell Differentiation; D002999:Clone Cells / Q000821:virology*; D006801:Humans; D051379:Mice; D009000:Monocytes / Q000473:pathology / Q000821:virology*; D010322:Parvoviridae Infections / Q000821:virology*; D017992:Parvovirus; D014779:Virus Replication