Early Alteration of Nucleocytoplasmic Traffic Induced by Some RNA Viruses

Abstract

A HeLa cell line expressing the green fluorescent protein fused to the SV40 T-antigen nuclear localization signal (EGFP-NLS) was established. Fluorescence in these cells was confined to the nuclei. After poliovirus infection, cytoplasmic fluorescence in a proportion of cells could be detected by 1 h postinfection (p.i.) and in virtually all of the fluorescent cells by 2 h p.i. The relocation could be prevented by cycloheximide but not by inhibition of poliovirus replication by guanidine. HCl. Nuclear exit of a protein composed of three copies of GFP fused to the NLS also occurred upon poliovirus infection. A similar redistribution of EGFP-NLS took place upon infection with coxsakievirus B3 and, to a lesser extent, with vesicular stomatitis virus. The EGFP-NLS efflux was not due to the loss of NLS. Thus, some positive-strand and negative-strand RNA viruses trigger a rapid nonspecific relocation of nuclear proteins.

Influenza Virus-Induced Caspase-Dependent Enlargement of Nuclear Pores Promotes Nuclear Export of Viral Ribonucleoprotein Complexes

“…For members of the family Picornaviridae, it has been shown that nuclear components, such as Nup153, may be cleaved by the viral 2A pro protein (51). In other cases, classical nuclear import pathways were found to be blocked, resulting in cytoplasmic retention (and accumulation) of nuclear cargo; also, increased diffusion limits by mechanisms that do not depend on caspase activation have been described to be induced in picornavirus-infected cells (51)(52)(53). In contrast to these picornavirus studies, our data suggest transfected with a plasmid that codes either for a GFP trimer that carries a nuclear localization signal (3xGFP) and accumulates in the nucleus or for a GFP pentamer that lacks a nuclear localization signal (5xGFP) and accumulates in the cytoplasm.…”

Nucleocytoplasmic Traffic Disorder Induced by Cardioviruses

“…For example, enteroviruses induce a bidirectional increase in permeability of the nuclear envelope accompanied by relocation of some nuclear proteins into the cytoplasm and cytoplasmic ones into the nucleus (8,9). This effect appears to be due to opening of the nuclear pores, as revealed by electron microscopy (10).…”

“…Two relevant mechanisms have been described. Poliovirus infection induces an increase in the bidirectional permeability of the nuclear envelope, apparently due to the destruction of nuclear pores, as visualized by electron microscopy (8,10). In addition, active nuclear import via different pathways is also impaired in cells infected with poliovirus and rhinovirus (34,35).…”

Functional Interaction of Heterogeneous Nuclear Ribonucleoprotein C with Poliovirus RNA Synthesis Initiation Complexes

“…In the present study, we investigated the possible role of the cellular protein hnRNP C in the process of PV RNA synthesis. During PV infection, this nuclear RNA-binding protein relocalizes to the cytoplasm due to alterations in nucleocytoplasmic trafficking (9,22,23). Interference with protein trafficking, through the disruption of import and induced efflux of nuclear proteins, may be an essential part of the picornavirus replicative cycle by providing abundant nuclear proteins in the cytoplasm that could function in translation, RNA synthesis, or packaging.…”

“…Belov et al have determined that PV infection increases nuclear envelope permeability, resulting in relocalization of nuclear proteins to the cytoplasm, as well as cytoplasmic proteins to the nucleus (9). The findings of Belov et al also indicated that PV-induced permeability does not require caspase-9, a protease that is involved in nuclear permeabilization during apoptosis.…”