title: The nonstructural proteins of Nipah virus play a key role in pathogenicity in experimentally infected animals.
abstract: Nipah virus (NiV) P gene encodes P protein and three accessory proteins (V, C and W). It has been reported that all four P gene products have IFN antagonist activity when the proteins were transiently expressed. However, the role of those accessory proteins in natural infection with NiV remains unknown. We generated recombinant NiVs lacking V, C or W protein, rNiV(V-), rNiV(C-), and rNiV(W-), respectively, to analyze the functions of these proteins in infected cells and the implications in in vivo pathogenicity. All the recombinants grew well in cell culture, although the maximum titers of rNiV(V-) and rNiV(C-) were lower than the other recombinants. The rNiV(V-), rNiV(C-) and rNiV(W-) suppressed the IFN response as well as the parental rNiV, thereby indicating that the lack of each accessory protein does not significantly affect the inhibition of IFN signaling in infected cells. In experimentally infected golden hamsters, rNiV(V-) and rNiV(C-) but not the rNiV(W-) virus showed a significant reduction in virulence. These results suggest that V and C proteins play key roles in NiV pathogenicity, and the roles are independent of their IFN-antagonist activity. This is the first report that identifies the molecular determinants of NiV in pathogenicity in vivo.
authors.affiliation: Laboratory Animal Research Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan. yone@ims.u-tokyo.ac.jp
authors.forename: Misako
authors.initials: M
authors.lastname: Yoneda
authors.forename: Vanessa
authors.initials: V
authors.lastname: Guillaume
authors.forename: Hiroki
authors.initials: H
authors.lastname: Sato
authors.forename: Kentaro
authors.initials: K
authors.lastname: Fujita
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Georges-Courbot
authors.forename: Fusako
authors.initials: F
authors.lastname: Ikeda
authors.forename: Mio
authors.initials: M
authors.lastname: Omi
authors.forename: Yuri
authors.initials: Y
authors.lastname: Muto-Terao
authors.forename: T Fabian
authors.initials: TF
authors.lastname: Wild
authors.forename: Chieko
authors.initials: C
authors.lastname: Kai
mesh_terms: D000818:Animals; D002460:Cell Line; D002522:Chlorocebus aethiops; D006224:Cricetinae; D045464:Henipavirus Infections / Q000821:virology*; D006801:Humans; D008647:Mesocricetus; D045405:Nipah Virus / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity*; D014709:Vero Cells; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D017361:Viral Nonstructural Proteins