The nonstructural proteins of the autonomous parvovirus minute virus of mice interfere with the cell cycle, inducing accumulation in G2

• Published in: Cell growth & differentiation Vol. 6; no. 7; pp. 781 - 787
• Main Authors: DE BEECK, A. O, ANOUJA, F, MOUSSET, S, ROMMELAERE, J, CAILLET-FAUQUET, P
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.07.1995
• Subjects: Animals; Biological and medical sciences; Cell Cycle - physiology; Cell Division - physiology; Cell Line, Transformed - cytology; Cell Line, Transformed - virology; Fibroblasts - virology; Flow Cytometry; Fluorescent Dyes; Fundamental and applied biological sciences. Psychology; G2 Phase - physiology; Gene Expression - physiology; Humans; Kidney - cytology; Microbiology; Minute Virus of Mice - chemistry; Minute Virus of Mice - genetics; Minute Virus of Mice - physiology; Rats; Rats, Inbred F344; Replicative cycle, interference, host-virus relations, pathogenicity, miscellaneous strains; Viral Nonstructural Proteins - toxicity; Virology; Virus; Pathogenicity; Parvovirus; Cell line; Parvoviridae; Transformed cell; Cell cycle; Cytopathology; Mechanism of action; Host virus relation; Mouse minute virus
• ISSN: 1044-9523; 2377-0732

The nonstructural (NS) proteins of the autonomous parvovirus minute virus of mice (prototype strain) are involved in viral DNA replication and in the regulation of parvoviral and heterologous promoters. By constructing cell lines having integrated the NS coding sequence under the control of an inducible promoter, we were able to demonstrate that NS proteins are toxic, once expressed in the transformed cells. Cell killing appears after several days of NS expression, suggesting that NS toxicity involved cellular factors. In this paper, we show that NS proteins are cytotoxic and interfere with the cell cycle in proliferating cells only NS expression is innocuous in resting cells, whereas in growing cells, it induces the accumulation of G2 cells. This cytostatic effect is enhanced upon neoplastic transformation, which sensitized the cells to NS killing. Moreover, as clones resistant to NS toxicity undergo no alteration of their cycle, this cytostatic effect of NS proteins could be an early step on the way to cell killing. These observations strongly suggest that NS toxicity involves cellular factors associated with the regulation of the cell cycle.