No abstract

Protoparvoviruses are simple single-stranded DNA viruses that infect many animal species. The protoparvovirus minute virus of mice (MVM) infects murine and transformed human cells provoking a sustained DNA damage response (DDR). This DDR is dependent on signaling by the ATM kinase and leads to a prolonged pre-mitotic cell cycle block that features the inactivation of ATR-kinase mediated signaling, proteasome-targeted degradation of p21, and inhibition of cyclin B1 expression. This review explores how protoparvoviruses, and specifically MVM, co-opt the common mechanisms regulating the DDR and cell cycle progression in order to prepare the host nuclear environment for productive infection.

Well-defined tissue tropism makes Autonomous Parvoviruses a valuable model for studies of virus-cell interactions and gene therapy research. We developed a new Minute Virus of Mice variant, different from the known prototype (MVMp) and immunosuppressive (MVMi) strains. The new virus variant, designated F1, was isolated from the culture of semi-permissive Fisher Rat Fibroblasts, F111, infected with MVMp. The F1 genome carried point mutations in regions known to determine the mutually restricted host ranges of MVMp and MVMi. In F111 cells, F1 cytotoxicity, gene expression and multiplication were significantly higher compared to MVMp. Conversely the wild-type virus propagated in MVMp-permissive cells more efficiently than the F1. Reversion of the F1-specific mutations to wild-type MVMp sequence, following reverse-passaging of the mutant virus in MVMp-permissive cells, confirmed a specific adaptation of the F1 virus to F111 cells. Considerable divergence in tissue specificities between the wild-type and mutant viruses was demonstrated in vivo.