THE NS1 PROTEIN OF THE AUTONOMOUS PARVOVIRUS MINUTE VIRUS OF MICE BLOCKS CELLULAR DNA-REPLICATION - A CONSEQUENCE OF LESIONS TO THE CHROMATIN

The nonstructural protein NS1 of the autonomous parvovirus minute viru s of mice interferes with cell division and can cause cell death, depe nding on the cell transformation state. Upon infection, the synthesis of NS1 protein is massively initiated during S phase. In this article, we show that minute virus of mice-infected cells accumulate in this p hase. To investigate the link between NS1 accumulation and S-phase arr est, we have used stably transfected cells in which NS1 expression is under the control of a glucocorticoid-inducible promoter (the long ter minal repeat of mouse mammary tumor virus), NS1 expression interferes with cell DNA replication, and consequently, the cell cycle stops in S phase, NS1 expression also induces nicks in the cell chromatin, as de tected by an in situ nick translation assay, The nicks are observed se veral hours before any cell cycle perturbation, As cell cycle arrest i s a common consequence of DNA damage, we propose that NS1 exerts its c ytostatic activity by inducing lesions in cell chromatin.