Measles virus-induced immunosuppression in vitro is associated with deregulation of G1 cell cycle control proteins.
Virus-induced immunosuppression is the major cause of the high morbidity/mortality rates associated with acute measles. It has been shown previously that mitogen-dependent proliferation of peripheral blood lymphocytes (PBL) was strongly impaired after contact with the measles virus (MV) glycoproteins F and H expressed on the surface of infected cells, cells transfected with the corresponding expression constructs or UV-inactivated MV (UV-MV). The state of unresponsiveness was not associated with the induction of apoptosis, and a significant proportion of PBL was found to be arrested in the G0/G1 phase of the cell cycle. It is now shown that cell cycle cessation, rather than complete arrest, is induced after MV glycoprotein contact. No obvious role was found for p53 in the induction of this unresponsiveness. With UV-MV as effector, downregulation of p27, an inhibitor of cyclin-dependent kinase (CDK)-cyclin complexes, was significantly delayed after mitogenic stimulation of human PBL. The activities of both CDK4/6-cyclin D and CDK2-cyclin E complexes for phosphorylation of exogenous substrates in vitro were strongly reduced. CDK4, CDK6, cyclins D3 and E and, to a minor extent, CDK2 failed to accumulate at the protein level after mitogenic stimulation in the presence of UV-MV. These data indicate that MV-induced proliferative unresponsiveness of PBL to mitogenic stimulation is associated with a drastic deregulation of the expression of cell cycle genes essential for the G1/S phase transition.
Engelking
O
O
Fedorov
L M
LM
Lilischkis
R
R
Ter Meulen
V
V
Schneider-Schaulies
S
S
D000328:Adult; D018797:Cell Cycle Proteins / Q000276:immunology*; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D016193:G1 Phase / Q000276:immunology; D006801:Humans; D007165:Immunosuppression Therapy; D008214:Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D008457:Measles / Q000276:immunology*; D008459:Measles virus
D018797:Cell Cycle Proteins