title: Newcastle disease virus (NDV)-based assay demonstrates interferon-antagonist activity for the NDV V protein and the Nipah virus V, W, and C proteins.
abstract: We have generated a recombinant Newcastle disease virus (NDV) that expresses the green fluorescence protein (GFP) in infected chicken embryo fibroblasts (CEFs). This virus is interferon (IFN) sensitive, and pretreatment of cells with chicken alpha/beta IFN (IFN-alpha/beta) completely blocks viral GFP expression. Prior transfection of plasmid DNA induces an IFN response in CEFs and blocks NDV-GFP replication. However, transfection of known inhibitors of the IFN-alpha/beta system, including the influenza A virus NS1 protein and the Ebola virus VP35 protein, restores NDV-GFP replication. We therefore conclude that the NDV-GFP virus could be used to screen proteins expressed from plasmids for the ability to counteract the host cell IFN response. Using this system, we show that expression of the NDV V protein or the Nipah virus V, W, or C proteins rescues NDV-GFP replication in the face of the transfection-induced IFN response. The V and W proteins of Nipah virus, a highly lethal pathogen in humans, also block activation of an IFN-inducible promoter in primate cells. Interestingly, the amino-terminal region of the Nipah virus V protein, which is identical to the amino terminus of Nipah virus W, is sufficient to exert the IFN-antagonist activity. In contrast, the anti-IFN activity of the NDV V protein appears to be located in the carboxy-terminal region of the protein, a region implicated in the IFN-antagonist activity exhibited by the V proteins of mumps virus and human parainfluenza virus type 2.
authors.affiliation: Department of Microbiology, Mount Sinai School of Medicine, New York, New York 10029, USA.
authors.forename: Man-Seong
authors.initials: MS
authors.lastname: Park
authors.forename: Megan L
authors.initials: ML
authors.lastname: Shaw
authors.forename: Jorge
authors.initials: J
authors.lastname: Muñoz-Jordan
authors.forename: Jerome F
authors.initials: JF
authors.lastname: Cros
authors.forename: Takaaki
authors.initials: T
authors.lastname: Nakaya
authors.forename: Nicole
authors.initials: N
authors.lastname: Bouvier
authors.forename: Peter
authors.initials: P
authors.lastname: Palese
authors.forename: Adolfo
authors.initials: A
authors.lastname: García-Sastre
authors.forename: Christopher F
authors.initials: CF
authors.lastname: Basler
mesh_terms: D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D002642:Chick Embryo; D002522:Chlorocebus aethiops; D017931:DNA Primers; D049452:Green Fluorescent Proteins; D007370:Interferon Type I / Q000037:antagonists & inhibitors*; D008164:Luminescent Proteins / Q000235:genetics; D009522:Newcastle disease virus / Q000502:physiology*; D010957:Plasmids; D014162:Transfection; D014709:Vero Cells; D014764:Viral Proteins / Q000235:genetics / Q000502:physiology*
chemical_list: D017931:DNA Primers; D007370:Interferon Type I; D008164:Luminescent Proteins; D014764:Viral Proteins; D049452:Green Fluorescent Proteins