RESUMEN
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.
Asunto(s)
Núcleo Celular/genética , Núcleo Celular/fisiología , Daño del ADN , Interacciones Huésped-Patógeno , Virus Diminuto del Ratón/fisiología , Parvovirus/fisiología , Animales , Ciclo Celular , Línea Celular , Ciclina B1/metabolismo , Humanos , Ratones , Mitosis , Transducción de Señal , Replicación ViralRESUMEN
The nuclear envelope (NE) is a vital structure that separates the nucleus from the cytoplasm. Because the NE is such a critical cellular barrier, many viral pathogens have evolved to modulate its permeability. They do this either by breaching the NE or by disrupting the integrity and functionality of the nuclear pore complex (NPC). Viruses modulate NE permeability for different reasons. Some viruses disrupt NE to deliver the viral genome into the nucleus for replication, while others cause NE disruption during nuclear egress of newly assembled capsids. Yet, other viruses modulate NE permeability and affect the compartmentalization of host proteins or block the nuclear transport of host proteins involved in the host antiviral response. Recent scientific advances demonstrated that other viruses use proteins of the NPC for viral assembly or disassembly. Here we review the ways in which various viruses affect NE and NPC during infection.
Asunto(s)
Membrana Nuclear/patología , Proteínas de Complejo Poro Nuclear/metabolismo , Poro Nuclear/patología , Virosis/patología , Virosis/virología , Virus/metabolismo , Membrana Nuclear/metabolismo , Membrana Nuclear/virología , Poro Nuclear/metabolismo , Poro Nuclear/virologíaRESUMEN
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.