title: Importance of rabies virus nucleoprotein in viral evasion of interferon response in the brain.
abstract: By using a cultured neuroblastoma cell line, the present authors recently showed that the N protein of virulent rabies virus fixed strain Nishigahara (Ni), but not that of the attenuated derivative Ni-CE, mediates evasion of induction of type I interferon (IFN). In this study, to determine whether Ni N protein indeed fulfills this function in vivo, the abilities to suppress IFN responses in the mouse brain of Ni-CE and the virulent chimeric virus CE(NiN), which has the N gene from Ni in the genetic background of Ni-CE, were compared. It was demonstrated that CE(NiN) propagates and spreads more efficiently than does Ni-CE in the brain and that IFN response in brains infected with CE(NiN) is weaker than in those infected with Ni-CE. It was also shown that amino acids at positions 273 and 394 in the N protein, which are known as pathogenic determinants, affect the ability of the viruses to suppress IFN response in the brain. These findings strongly suggest that, in the brain, rabies virus N protein plays important roles in evasion of innate immune responses and thereby in efficient propagation and spread of virus leading to lethal outcomes of infection.
authors.affiliation: United Graduate School of Veterinary Sciences, Laboratory of Zoonotic Diseases, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan.
authors.forename: Tatsunori
authors.initials: T
authors.lastname: Masatani
authors.forename: Naoto
authors.initials: N
authors.lastname: Ito
authors.forename: Yuki
authors.initials: Y
authors.lastname: Ito
authors.forename: Keisuke
authors.initials: K
authors.lastname: Nakagawa
authors.forename: Masako
authors.initials: M
authors.lastname: Abe
authors.forename: Satoko
authors.initials: S
authors.lastname: Yamaoka
authors.forename: Kota
authors.initials: K
authors.lastname: Okadera
authors.forename: Makoto
authors.initials: M
authors.lastname: Sugiyama
mesh_terms: D000818:Animals; D001921:Brain / Q000276:immunology* / Q000821:virology*; D002460:Cell Line; D005260:Female; D057131:Immune Evasion; D007150:Immunohistochemistry; D007372:Interferons / Q000037:antagonists & inhibitors*; D051379:Mice; D008853:Microscopy; D019590:Nucleocapsid Proteins / Q000378:metabolism*; D011820:Rabies virus / Q000276:immunology* / Q000502:physiology*; D019562:Viral Load
chemical_list: D019590:Nucleocapsid Proteins; C099601:nucleocapsid protein, Rabies virus; D007372:Interferons
keywords: brain; innate immunity; nucleoprotein; rabies virus