title: Poliovirus type 1 infection of murine PRNP-knockout neuronal cells.
abstract: Transfection of the prion protein gene (Prnp) into prion-deficient mouse cells was shown to reduce the replication of coxsackievirus B3, an enterovirus. Because mice can be susceptible to poliovirus infection by parenteral routes, the authors tested the susceptibility to poliovirus-1 (PV-1) of a panel of murine neuronal cell lines differing in their ability to express Prnp. The investigated cell lines (prionless HpL3.4 cells, HpL3.4 cells transfected with a Prnp vector, HpL3.4 cells transfected with a void vector, wild-type Hw3.5 Prnp(+/+) cells) expressed the murine homologue (Tage4) of human poliovirus receptor (CD155/hPVR). PV-1 infection of Prnp(-/-) HpL3.4 cells resulted in the production of high viral titers, though viral antigens could be detected in only 0.5% to 2% of cells. Wild-type Prnp(+/+) cells and prionless cells transfected with the Prnp gene were not permissive to PV-1. Results of viral titration and immunofluorescence were confirmed by conventional polymerase chain reaction (PCR) and quantitative real-time PCR. Exposure to PV-1 had no influence on the gene expression profile of Prnp(+/+) cells. In contrast, PV-1 infection was associated with upregulation of several genes in permissive Prnp(-/-) cell cultures: type I interferon (IFN) genes, IFN-related developmental regulator 1 (IFNRD1), tumor necrosis factor superfamily member 13b (TNFSF13b), interleukin (IL) - 7, granulocyte/macrophage colony-stimulating factors (CSFs), hepatocyte growth factor (HGF), vascular endothelial growth factor-A, transforming growth factors beta1 and beta3 (TGFb1, TGFb3), as well as a variety of bone morphogenetic proteins endowed with neuroprotective activity. Distinction of permissive from nonpermissive neuronal cells on the basis of Prnp expression suggests that prion-deficient mice could represent an extraordinarily sensitive animal model for poliovirus infection.
authors.affiliation: Department of Clinical and Biological Sciences, University of Insubria, Varese, Italy.
authors.forename: Andreina
authors.initials: A
authors.lastname: Baj
authors.forename: Alessia
authors.initials: A
authors.lastname: Bettaccini
authors.forename: Takuya
authors.initials: T
authors.lastname: Nishimura
authors.forename: Takashi
authors.initials: T
authors.lastname: Onodera
authors.forename: Antonio
authors.initials: A
authors.lastname: Toniolo
mesh_terms: D000818:Animals; D002460:Cell Line; D004195:Disease Models, Animal; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000821:virology*; D011051:Poliomyelitis / Q000821:virology*; D017955:Poliovirus / Q000502:physiology*; D011328:Prions / Q000235:genetics; D014162:Transfection
chemical_list: D011328:Prions