Premium
Importance of rabies virus nucleoprotein in viral evasion of interferon response in the brain
Author(s) -
Masatani Tatsunori,
Ito Naoto,
Ito Yuki,
Nakagawa Keisuke,
Abe Masako,
Yamaoka Satoko,
Okadera Kota,
Sugiyama Makoto
Publication year - 2013
Publication title -
microbiology and immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.664
H-Index - 70
eISSN - 1348-0421
pISSN - 0385-5600
DOI - 10.1111/1348-0421.12058
Subject(s) - rabies virus , biology , nucleoprotein , virology , virus , interferon , virulence , immune system , rabies , innate immune system , gene , immunology , genetics
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.